2. UREMIA
Azotemia refers to high levels of urea but is used primarily
when the abnormality can be measured chemically but is not yet
so severe as to produce symptoms.
Uremia is the pathological manifestations of severe azotemia.
There is no specific time for the onset of uremia for people with
progressive loss of kidney function.
Both uremia and the uremic syndrome have been used
interchangeably to define a very high plasma urea concentration
that is the result of renal failure
3. INTRODUCTION
All patients with renal disease should undergo an assessment of
renal function by estimating (GFR) from ser creatinine.
This measurement is used clinically
to evaluate the degree of renal impairment,
to follow the course of the disease, and
to assess the response to therapy.
An attempt must also be made to obtain a specific diagnosis.
careful urinalysis, kidney ultrasound, referral to a nephrologist,
and a kidney biopsy.
4. IDENTIFICATION OF RISK FACTORS AND STAGING OF
CKD
Risk factors:
1. hypertension,
2. diabetes mellitus,
3. autoimmune disease,
4. older age,
5. a family history of renal disease,
6. a previous episode of acute kidney injury,
7. Kidney donors and transplant recipients
8. and the presence of
a. proteinuria,
b. abnormal urinary sediment, or
c. structural abnormalities of the urinary tract
5. CALCULATION OF GFR
Methods of calculation
Cockcroft-Gault formula
MDRD formula/modified MDRD
CKD-EPI when eGFR values above 60 ml/min/1.7 sq meter
is desired
This CKD-EPI equation calculator should be used when Scr
 reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2
 are desired
This CKD-EPI equation calculator should be used when Scr
 reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2
 are desired
This CKD-EPI equation calculator should be used when Scr
 reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2
 are desired
This CKD-EPI equation calculator should be used when Scr
 reported in mg/dL. This equation is recommended when eGFR values above 60 mL/min/1.73 m2
 are desire
7. 84 F 22 M 66 M 66 F
⢠Wt (kg) 45.5 104.5 77.2
71.8
⢠Screat 1.2 1.2 1.2 1.2
⢠eGFR 26.9 142.7 66.1 52.3
(Calculated with Cockcroft-Gault)
8. ⢠MDRD GFR Formula*
170 x [SCr]-0.999
x [Age]-0.176
x
[0.762 if female] x [1.180 if
black] x [Alb]+0.318
⢠Modified MDRD
Formula
186.338 x [SCr]-1.154
x [Age]-0.203
x
[1.212 if black] x [0.742 if
female]
MDRD GFR
*From Levey et al, 1999
Ann Intern Med 130: 461-470
(A calculator may be found at
www.hdcn.org)
10. HOW THE KIDNEY RESPONDS TO INJURY?
The 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 RI often has a normal or near-
normal ser creatinine.
Additional homeostatic mechanisms (most frequently occurring
within the renal tubules) permit the serum concentrations of
sodium, potassium, calcium, and phosphorous and the total body
water to also remain within the normal range.
11. PHYSIOLOGIC CHANGES IN CHRONIC
KIDNEY DISEASE
Increased single nephron GFR
Afferent arteriolar vasodilation
Intraglomerular hypertension
Loss of glomerular permselectivity
Inabilty to appropriately dilute or concentrate the urine
in the face of volume challenge
12. PHYSIOLOGIC CHANGES IN CHRONIC
KIDNEY DISEASE
Intraglomerular hypertension and glomerular hypertrophy
leading to glomerular scarring (glomerulosclerosis).
Additional causes may include systemic hypertension,
hyperlipidemia, metabolic acidosis, and tubulointerstitial disease.
Thus, proteinuria typically is present in patients with progressive
CKD, even in primary tubulointerstitial diseases such as reflux
nephropathy.
Principal targets for renal protection âthe blood pressure goal
and, the proteinuria goal
13. PHYSIOLOGIC CHANGES IN CKD
- ACE inhibitors or ARBs agents in patients with
proteinuric CKD if begun before irreversible scarring
- ARBs do not appear to be more beneficial than other
antihypertensive agents in patients with nonproteinuric
CKD.
- When used in patients with CKD, common side
effects of ARBs include a mild to moderate reduction in
GFR and hyperkalemia, which occurs soon after the
initiation of therapy or an increase in dose
14. PATHOGENESIS OF SECONDARY
GLOMERULOSCLEROSIS
Nephron Mass
Glomerular Volume and
Glomerular Hypertension
Epithelial Cell Density and
Foot Process Fusion
Glomerular Sclerosis
and Hyalinosis
Primary Insult
Proteinuria
15. LEFT: SCHEMA OF THE NORMAL GLOMERULAR
ARCHITECTURE.
RIGHT: SECONDARY GLOMERULAR CHANGES
16. PHYSIOLOGIC CHANGES IN CKD
The gradual decline in function in patients with (CKD)
is initially asymptomatic.
However, different signs and symptoms may be
observed with advanced RF, including volume overload,
hyperkalemia, metabolic acidosis, hypertension, anemia,
and (MBDs).
The onset of (ESRD) results in a constellation of signs
and symptoms referred to as uremia.
17. WHAT IS CKD?
Chronic kidney disease is defined based on the presence of either
kidney damage or decreased kidney function for three or more
months, irrespective of cause.
⢠Criteria:
Duration âĽ3 months, based on documentation or inference
Glomerular filtration rate (GFR) <60 mL/min/1.73 m2
Kidney damage, as defined by structural abnormalities or functional abnormalities
other than decreased GFR
18. CHRONIC KIDNEY DISEASE
A) Pathologic abnormalities (examples). Cause is based on underlying illness and
pathology. Markers of kidney damage may reflect pathology.
1.Glomerular diseases (diabetes, autoimmune diseases, systemic infections, drugs,
neoplasia)
2.Vascular diseases (atherosclerosis, hypertension, ischemia, vasculitis, thrombotic
microangiopathy)
3.Tubulointerstitial diseases (urinary tract infections, stones, obstruction, drug
toxicity)
4.Cystic disease (polycystic kidney disease)
Kidney damage, as defined by structural abnormalities or functional abnormalities other than
decreased GFR
19. CHRONIC KIDNEY DISEASE
B) History of kidney transplantation. In addition to pathologic
abnormalities observed in native kidneys, common pathologic
abnormalities include the following:
1.Chronic allograft nephropathy (non-specific findings of tubular
atrophy, interstitial fibrosis, vascular and glomerular sclerosis)
2.Rejection
3.Drug toxicity (calcineurin inhibitors)
4.BK virus nephropathy
5.Recurrent disease (glomerular disease, oxalosis, Fabry disease)
Kidney damage, as defined by structural abnormalities or functional abnormalities other
than decreased GFR
20. CHRONIC KIDNEY DISEASE
C) Albuminuria as a marker of kidney damage (increased glomerular
permeability, urine albumin-to-creatinine ratio [ACR] >30 mg/g).*
1.The normal urine ACR in young adults is <10 mg/g. Urine ACR
categories 10-29, 30-300 and >300 mg are termed "high normal, high,
and very high" respectively. Urine ACR >2200 mg/g is accompanied by
signs and symptoms of nephrotic syndrome
2.Threshold value corresponds approximately to urine dipstick values of
trace or 1+
3.High urine ACR can be confirmed by urine albumin excretion in a timed
urine collection
Kidney damage, as defined by structural abnormalities or functional abnormalities other
than decreased GFR
21. CHRONIC KIDNEY DISEASE
D) Urinary sediment abnormalities as markers of kidney damage
1.RBC casts in proliferative glomerulonephritis
2.WBC casts in pyelonephritis or interstitial nephritis
3.Oval fat bodies or fatty casts in diseases with proteinuria
4.Granular casts and renal tubular epithelial cells in many
parenchymal diseases (non-specific)
Kidney damage, as defined by structural abnormalities or functional abnormalities other
than decreased GFR
22. CHRONIC KIDNEY DISEASE
E) Imaging abnormalities as markers of kidney damage (ultrasound,
computed tomography and magnetic resonance imaging with or without
contrast, isotope scans, angiography).
1.Polycystic kidneys
2.Hydronephrosis due to obstruction
3.Cortical scarring due to infarcts, pyelonephritis or vesicoureteral reflux
4.Renal masses or enlarged kidneys due to infiltrative diseases
5.Renal artery stenosis
6.Small and echogenic kidneys (common in later stages of CKD due to
many parenchymal diseases)
Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR
23.
24. ETIOLOGY OF CHRONIC KIDNEY DISEASE
Diabetes
43%
HTN
25%
GN
12%
Other
20%
Diabetes
HTN
GN
Other
25. CHRONIC KIDNEY DISEASE
No direct correlation exists between the absolute serum levels
of (BUN) or creatinine and the development of uremic
symptoms.
Some patients have relatively low levels (eg, a BUN of 60 mg/dL
in an older patient) but are markedly symptomatic, while others
have marked elevations (eg, a BUN of 140 mg/dL]) but remain
asymptomatic.
26. CHRONIC KIDNEY DISEASE
Certain drugs also interfere with either creatinine
secretion or the assay used to measure the serum
creatinine. These include cimetidine, trimethoprim,
cefoxitin, and flucytosine.
In these settings,
There will be no change in the true GFR;
Absence of a concurrent elevation in the (BUN)
29. CLINICAL ABNORMALITIES IN UREMIA
1. Fluid and electrolyte disturbances
2. Endocrine-metabolic disturbances
3. Neuromuscular disturbances
4. Cardiovascular and pulmonary disturbances
5. Dermatologic disturbances
6. Gastrointestinal disturbances
7. Hematologic and immunologic disturbances
(I) improves with an optimal program of dialysis and related
therapy;
(P) persist or even progress, despite an optimal program; (D)
develops only after initiation of dialysis therapy.
30. CLINICAL ABNORMALITIES IN UREMIA
1. Fluid and electrolyte disturbances
a. Volume expansion (I)
b. Hyponatremia (I)
c. Hyperkalemia (I)
d. Hyperphosphatemia (I)
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
31. FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS
Hyponatremia â water restriction
ECFV expansion â salt restriction
Thiazides â limited utility in stages 3-5 CKD
- loop diuretics needed
Loop Diuretics resistance â Higher doses
Metolazone â combined with loop diuretics, which inhibits the
sodium chloride co-transporter of the distal convoluted tubule, can help
effect renal salt excretion
32. FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS
⢠HYPERKALEMIA
⢠Precipitated by
⢠increased dietary potassium intake,
⢠protein catabolism,
⢠hemolysis,
⢠hemorrhage,
⢠transfusion of stored red blood cells,
⢠and metabolic acidosis
⢠Medications .
33. FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS
Hyperkalemia
A common reason for initiation of RRT
There is limited K excretion as GFR falls
Diabetics may have a type IV RTA (hyporeninemic
hypoaldosteronism)
Use of ACE-I can exacerbate hyperkalemia
34. FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS
Hyperkalemia
- Potassium balance usually remains intact
until GFR < 10-20 mL/min
- Tx of acute hyperkalemia involves cardiac
monitoring, IV calcium chloride or
gluconate, insulin with glucose, bicarbonate,
and potassium-binding resins
- Chronic hyperkalemia txâd with dietary k
restriction, and Ca resonium PRN
35. FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS
Hypokalemia:
⢠Not common in CKD
⢠reduced dietary potassium intake
⢠GI losses
⢠Diuretic therapy
⢠Fanconiâs syndrome
⢠RTA
⢠Hereditary or acquired Tubulointerstitial disease
36. FLUID, ELECTROLYTE,AND ACID-BASE DISORDERS
Metabolic acidosis
⢠common disturbance in advanced CKD
⢠combination of hyperkalemia and hyperchloremic
metabolic acidosis is often present, even at earlier
stages of CKD (stages 1â3)
⢠Treat hyperkalemia
⢠the pH is rarely <7.35
⢠usually be corrected with oral sodium bicarbonate
supplementation
37. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
2. Endocrine-metabolic disturbances
38. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
2. Endocrine-metabolic disturbances
39. PTH
Pi Ca2+
Renal Mass
25(OH)D3 1,25(OH)2D3
1-alpha-hydroxylase1-alpha-hydroxylase
+
Acidosis
+
Hyperparathyroid Related Bone Disease
Impaired
Absorption
Osteitis Fibrosa
Cystica
41. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
Other complications of abnormal mineral
metabolism:
⢠Calciphylaxis (calcific uremic arteriolopathy)
⢠Other etiologies
⢠use of oral calcium as a phosphate binder
⢠Warfarin
42. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
2. Endocrine-metabolic disturbances
43. CKD patients have a nutritional deficiency of 25-OH Vitamin D
which itself leads to an increase in PTH secretion
Levels of 25-OH D should be measured when PTH-Intact
>70pg/ml
Treatment
<5ng/ml 50,000U Ergocalciferol/wk x12, then q mo x6
5-15ng/ml 50,000/wk x 4, then q mo x 6
16-30ng/ml 50,000/month x 6
Measure 25(OH)-D at 6 months
Maintenance 800-1200 IU qd
Calcium and Phosphorus Balance:
Recommendations (KDOQI)
44. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
The principal complications of abnormalities of calcium and
phosphate metabolism in CKD
1. occur in the skeleton and
2. the vascular bed,
3. with occasional severe involvement of extraosseous soft
tissues
Bone manifestations of CKD, classified as:
⢠associated with high bone turnover with increased PTH
levels
⢠low bone turnover with low or normal PTH levels
45. DISORDERS OF CALCIUM AND PHOSPHATE
METABOLISM
The principal complications of abnormalities of calcium and
phosphate metabolism in CKD
1. occur in the skeleton and
2. the vascular bed,
3. with occasional severe involvement of extraosseous soft
tissues
Bone manifestations of CKD, classified as:
⢠associated with high bone turnover with increased PTH
levels
⢠low bone turnover with low or normal PTH levels
46. COMPLICATIONS OF LONGTERM CALCIUM
AND PHOSPHORUS IMBALANCE
Tertiary hyperparathyroidism
Renal osteodystrophy
Demineralization
Bone pain
Fractures
Systemic toxicity
Cutaneous - Calciphylaxis
Cardiovascular, accelerated vascular
calcification
47. How are these goals achieved ?
Control of dietary phosphorus intake to 0.8-1g/d
May need initiation of âPhosphate bindersâ with
meals
When 25(OH)-D < 30pg/ml and PTH-I > target,
initiate treatment with exogenous âActive Vitamin
Dâ
A few patients with very elevated PTH-I values
may benefit from Calcimimetics
Calcium and Phosphorus Balance
KDOQI Recommendations
48. The use of calcium based binders is now falling out of
favor because of the recognition of accelerated
vascular calcification proposed to be associated with
them.
Although controversial, this is thought by some to be
associated with the development of coronary
atherosclerosis and is related to the presence and/or
consequences of elevated serum phosphorus, calcium,
and (PTH)
Calcium and Phosphorus Balance
51. 13C.1 Adynamic bone disease in stage 5 CKD (as
determined either by bone biopsy or intact PTH <100
pg/ml [11.0 pmol/L]) should be treated by allowing
plasma levels of intact PTH to rise in order to increase
bone turnover. (OPINION)
13C.1a This can be accomplished by decreasing doses
of calcium-based phosphate binders and vitamin D or
eliminating such therapy. (OPINION)
Adynamic bone disease
52. Indication
Bio-Intact PTH > 800 pg/mL refractory to medical
therapy
Severe hypercalcemia
Progressive high turnover bone disease
Complications
May result in excessive low PTH levels
Symptomatic hypocalcemia
Risk for injury to recurrent laryngeal nerve
Parathyroidectomy
53. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
3. Neuromuscular disturbances
54. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances
55. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances
56. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances
57. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances
58. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances
59. CLINICAL ABNORMALITIES IN UREMIA
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
4. Cardiovascular and pulmonary disturbances
60. CARDIOVASCULAR ABNORMALITIES
Ischemic vascular disease
The CKD-related risk factors comprise
1. anemia,
2. hyperphosphatemia,
3. hyperparathyroidism,
4. sleep apnea, and
5. generalized inflammation
Cardiac troponin levels are frequently elevated in
CKD without evidence of acute ischemia.
61. CLINICAL ABNORMALITIES IN UREMIA
1.Pallor (I)b
2.Hyperpigmentation (I, P, or D)
3.Pruritus (P)
4.Ecchymoses (I)
5.Nephrogenic fibrosing dermopathy (D)
6.Uremic frost (I)
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
5. Dermatologic disturbances
62. CLINICAL ABNORMALITIES IN UREMIA
1.Anorexia (I)
2.Nausea and vomiting (I)
3.Gastroenteritis (I)
4.Peptic ulcer (I or P)
5.Gastrointestinal bleeding (I, P, or D)
6.Idiopathic ascites (D)
7.Peritonitis (D)
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
6. Gastrointestinal disturbances
63. IDIOPATHIC ASCITES
Ascites in ESKD patients is predominantly of the low SAAG and
high protein variety which is a manifestation of the combined
effect of altered peritoneal membrane permeability, fluid
overload and under-dialysis.
The severity of ascites is affected by the presence of concomitant
cardiac failure and hypoalbuminemia.
Investigations to rule out tuberculosis, if the clinical and
laboratory based suspicion is strongly in favour of this diagnosis.
65. CLINICAL ABNORMALITIES IN UREMIA
1.Anemia (I)b
2.Lymphocytopenia (P)
3.Bleeding diathesis (I or D)b
4.Increased susceptibility to infection
5.(I or P)
6.Leukopenia (D)
7.Thrombocytopenia (D)
(I) improves with an optimal program of dialysis and related therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.
7. Hematologic and immunologic disturbances
66. HEMATOLOGIC ABNORMALITIES
Anemia
A normocytic, normochromic anemia develops when
the GFR decreases to < 30-35 ml/min :
decreasing production of erythropoietin
Reduced renal mass
Uremic inhibition of bone marrow
Decreased RBC life-span
PTH induced marrow fibrosis
Iron deficiency
Folate or vitamin B12 deficiency
Aluminum related bone disease
67. The 2012 KDIGO guidelines,
Patients who do not have anemia, Hgb should be
checked when it is clinically indicated and at least
yearly
Patients with stage 3 CKD at least every six months
Patients with stage 4 to 5 CKD, at least every three
months
Patients with stage 5D should be monitored monthly.
68. Investigations
Nonrenal causes of anemia.
Red blood cell indices,
Absolute reticulocyte count,
Serum iron, total iron-binding capacity, percent
Transferrin saturation, serum ferritin,
White blood cell count and differential, platelet count,
B12 and folate if (MCV) is increased,
Ocult blood in stool.
This work-up should be performed prior to
administering ESA therapy.
69. HEMATOLOGIC ABNORMALITIES
Abnormal hemostasis
1. prolonged bleeding time,
2. decreased activity of platelet factor III,
3. abnormal platelet aggregation and adhesiveness,
4. and impaired prothrombin consumption.
Clinical manifestations include
1. an increased tendency to bleeding and bruising,
2. prolonged bleeding from surgical incisions,
3. menorrhagia,
4. and spontaneous GI bleeding
70. Balancing the impact of decreased protein intake on
the rate of progression of renal disease, against
hypoalbuminemia and malnutrition
Can we restrict protein intake sufficiently, without
leading to malnutrition, especially important in patients
with eGFR < 25 ml/min
Nutrition
71. common in patients with advanced CKD because of
a lower food intake (principally due to anorexia),
decreased intestinal absorption and digestion, and
metabolic acidosis
Many additional studies have shown a strong
correlation between malnutrition and death in
maintenance dialysis patients.
To best assess nutritional status, the serum albumin
and BW should be measured serially; these should be
measured approximately every one to three months
and more frequently, if necessary
Malnutrition
72. Patients with CKD are at increased risk for infection
The risk of bacterial infection (particularly pulmonary
and genitourinary) increases with the decline in kidney
function .
Preventive measures such as influenza and
pneumococcal immunization
Infection and vaccination
73. 2012 KDIGO guidelines :
âAdults with all stages of CKD should be offered annual vaccination with
influenza virus unless contraindicated.
Adults with stage 4 and 5 CKD who are at high risk of progression ofâ
CKD should be immunized against hepatitis B and the response
confirmed by immunologic testing.
Adults with CKD stages 4 and 5 should be vaccinated with polyvalentâ
pneumococcal vaccine unless contraindicated.
Patients who have received pneumococcal vaccination should be offered
revaccination within five years.
US has recommended two forms of pneumococcal vaccine, including
(PPSV23 [Pneumovax or Pnu-Immune]) and the (PCV13 [Prevnar for
individuals aged âĽ19 years with an immunocompromising condition,
including CKD
Vaccination
74. The primary finding in CKD is hypertriglyceridemia, with the total
cholesterol concentration usually being normal (perhaps due in part to
malnutrition in some patients).
2013 KDIGO guidelines that recommend an initial evaluation with lipid
profile, including total cholesterol, (LDL-C), (HDL-C), and triglycerides
As per the KDIGO guidelines, follow-up evaluation of lipid profiles is
generally not necessary for patients age âĽ50 years since statin therapy is
not titrated to the lipid profile.
Dyslipidemia
75. Follow-up testing may be performed among patients who are age
<50 years who are not already on a statin
Follow-up evaluation may also be performed
to assess adherence to statin treatment,
if there is a change in the modality of renal replacement therapy,
or
if there is concern about new secondary causes of dyslipidemia.
Dyslipidemia
77. Patients with (CKD) should be referred to a nephrologist when (eGFR)
is <30 mL/min/1.73 m2 in order to discuss and potentially plan for renal
replacement therapy.
There is less consensus about referral for patients with higher eGFRs.
Lower costs and/or decreased morbidity and mortality may be
associated with early referral and care by nephrologists
REFERRAL TO NEPHROLOGISTS
78. ďŽ Poorly controlled HTNPoorly controlled HTN
ďŽ Diabetes mellitus with atypical renal manifestationsDiabetes mellitus with atypical renal manifestations
ďŽ Proteinuria or nephrotic syndrome without retinopathyProteinuria or nephrotic syndrome without retinopathy
ďŽ Renal insufficiency without proteinuria or retinopathyRenal insufficiency without proteinuria or retinopathy
ďŽ Sudden onset of nephrotic syndrome or rapidly changing serumSudden onset of nephrotic syndrome or rapidly changing serum
creatininecreatinine
ďŽ Systemic disease associated with renal involvementSystemic disease associated with renal involvement
ďŽ Heavy proteinuriaHeavy proteinuria
ďŽ Urine-sediment abnormalitiesUrine-sediment abnormalities
ďŽ PriorPrior to onset of uremic symptomsto onset of uremic symptoms
REFERRAL TO NEPHROLOGISTS
79. In most studies, referral to the nephrologist is considered late if it is
within one to six months of the requirement for renal replacement
therapy .
25 to 50 percent of patients beginning chronic renal replacement
therapy in US required dialysis within one month of their first
nephrology visit ,
22 to 49 percent of patients were first seen by a nephrologist less than
four months prior to the initiation of dialysis
REFERRAL TO NEPHROLOGISTS
80. One retrospective study has suggested that a multidisciplinary
approach may improve survival .
The 2012 (KDIGO) CKD guidelines suggest management of
CKD patients in a multidisciplinary setting, with access to dietary
counseling, renal replacement therapies, transplant options,
vascular access surgery, and ethical, psychological and social
care .
REFERRAL TO NEPHROLOGISTS
81. âPericarditis or pleuritis (urgent indication).
Progressive uremic encephalopathy or neuropathy, (urgent indication).â
A clinically significant bleeding diathesis attributable to uremia (urgentâ
indication).
Fluid overload refractory to diuretics.â
âHypertension poorly responsive to antihypertensive medications.
Persistent metabolic disturbances that are refractory to medicalâ
therapy.
âPersistent nausea and vomiting.
Evidence of malnutrition.â
Indications for renal replacement
therapy
82. The timing of initiation of dialysis is unclear
To help avoid the onset of possible life-threatening
complications of uremia, the initiation of dialysis
should be considered in the asymptomatic patient with
an extremely low eGFR.
However, some clinicians may choose to closely
monitor (weekly) even when the eGFR is less than 8
to 10 mL/min/1.73 m2, with the initiation of dialysis
upon the onset of uremic signs/symptoms.
Asymptomatic patients with progressive
CKD
83. Dialysis provided evidence for the validity of the
intoxication :
Visual Evidence: uremic frost disappeared
Comatose patients were waking up
Survival was increased
What we see today is a different life-threatening
condition that is known as the âresidual uremic
syndromeâ
The âResidualâ Syndrome
84. A. Accumulation of:
1. large molecular weight solutes that are difficult to
remove by dialysis
2. protein-bound small molecular weight solutes that are
difficult to remove by dialysis
3. dialyzable solutes that are incompletely removed
B. Indirect phenomena:
1. Accelerated protein âagingâ
2. Inflammation
3. Tissue calcification
4. Toxic effect of hormone imbalance
C. A toxic effect of the dialysis itself
Possible Causes of the âResidualâ
Syndrome
85. Subtle signs of malnutrition
Increased susceptibility to infection
Increased susceptibility to cardiovascular complications
Low-grade serositis
Impaired vascular reactivity
Hypothermia
Reduced exercise capacity and O2 utilization
Fatigue
Subtle psychological disturbances such as loss of focus and
ambition (or is it depression?)
Sleep disturbances
Restless Legs
Clinical Manifestations of the âResidualâ
Syndrome
86. Uremia is the pathological manifestations of severe azotemia.
All patients with renal disease should undergo an assessment of
renal function
Chronic kidney disease is defined based on the presence of either
kidney damage or decreased kidney function for three or more
months, irrespective of cause.
No direct correlation exists between the absolute serum levels
of (BUN) or creatinine and the development of uremic
symptoms.
Lower costs and/or decreased morbidity and mortality may be
associated with early referral and care by nephrologists
Â
Conclusion
People with [GFR] between 50 and 60 mL and 30 years of age may have uremia to a degree. This means an estimated 8 million people in the United States with a GFR of less than 60 mL have uremic symptoms.
The symptoms, such as fatigue, can be very vague, making the diagnosis of impaired renal function difficult.
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
GFR can be assessed by the renal clearance of a substance
Clearance of substance X (Cx) = UxVx/Sx
Recall GFR * Sx = UxVx
(amount filtered = amount excreted)
Cx = UxV/Sx
Cx = GFR
Two important assumptions:
Marker neither secreted or absorbed
Steady state
Examples of markers: inulin, iothalamate, iohexol, serum creatinine, cystatin-C
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
Glomerular hypertrophy
Focal segmental glomerulosclerosis with hyalinosis
Interstitial fibrosis
Vascular sclerosis
Epithelial foot process fusion
Glomerular hypertrophy
Focal segmental glomerulosclerosis with hyalinosis
Interstitial fibrosis
Vascular sclerosis
Epithelial foot process fusion
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
Figure 280-1 Left: Schema of the normal glomerular architecture.
Right: Secondary glomerular changes associated with a reduction in nephron number, including enlargement of capillary lumens and focal
adhesions, which are thought to occur consequent to compensatory hyperfiltration and hypertrophy in the remaining nephrons.
It is important to identify factors that increase the risk for CKD, even in individuals with normal GFR.
Risk factors include hypertension, diabetes mellitus, autoimmune disease, older age, African ancestry, a family history of renal disease, a previous episode of acute kidney injury, and the presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract.
The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease.
Kidney damage refers to pathologic abnormalities, whether established via renal biopsy or imaging studies, or inferred from markers such as urinary sediment abnormalities or increased rates of urinary albumin excretion.
Decreased kidney function refers to a decreased glomerular filtration rate (GFR), which is usually estimated (eGFR) using serum creatinine and one of several available equations.
Pathologic abnormalities (examples). Cause is based on underlying illness and pathology. Markers of kidney damage may reflect pathology.
Glomerular diseases (diabetes, autoimmune diseases, systemic infections, drugs, neoplasia)
Vascular diseases (atherosclerosis, hypertension, ischemia, vasculitis, thrombotic microangiopathy)
Tubulointerstitial diseases (urinary tract infections, stones, obstruction, drug toxicity)
Cystic disease (polycystic kidney disease)
B) History of kidney transplantation. In addition to pathologic abnormalities observed in native kidneys, common pathologic abnormalities include the following:
Chronic allograft nephropathy (non-specific findings of tubular atrophy, interstitial fibrosis, vascular and glomerular sclerosis)
Rejection
Drug toxicity (calcineurin inhibitors)
BK virus nephropathy
Recurrent disease (glomerular disease, oxalosis, Fabry disease)
C) Albuminuria as a marker of kidney damage (increased glomerular permeability, urine albumin-to-creatinine ratio [ACR] &gt;30 mg/g).*
The normal urine ACR in young adults is &lt;10 mg/g. Urine ACR categories 10-29, 30-300 and &gt;300 mg are termed &quot;high normal, high, and very high&quot; respectively. Urine ACR &gt;2200 mg/g is accompanied by signs and symptoms of nephrotic syndrome (low serum albumin, edema and high serum cholesterol).
Threshold value corresponds approximately to urine dipstick values of trace or 1+, depending on urine concentration
High urine ACR can be confirmed by urine albumin excretion in a timed urine collection
D) Urinary sediment abnormalities as markers of kidney damage
RBC casts in proliferative glomerulonephritis
WBC casts in pyelonephritis or interstitial nephritis
Oval fat bodies or fatty casts in diseases with proteinuria
Granular casts and renal tubular epithelial cells in many parenchymal diseases (non-specific)
E) Imaging abnormalities as markers of kidney damage (ultrasound, computed tomography and magnetic resonance imaging with or without contrast, isotope scans, angiography).
Polycystic kidneys
Hydronephrosis due to obstruction
Cortical scarring due to infarcts, pyelonephritis or vesicoureteral reflux
Renal masses or enlarged kidneys due to infiltrative diseases
Renal artery stenosis
Small and echogenic kidneys (common in later stages of CKD due to many parenchymal diseases)
GFR and albuminuria grid to reflect the risk of progression by intensity of coloring (green, yellow, orange, red, deep red).
The numbers in the boxes are a guide to the frequency of monitoring (number of times per year).
Reprinted by permission from: Macmillan Publishers Ltd: Kidney International. KDIGO. Summary of recommendation statements. Kidney Int 2013; 3(Suppl):5. Copyright Š 2013.http://www.nature.com/ki/index.html.
Graphic 59716 Version 6.0
In summary, the pathophysiology of the uremic syndrome can be divided into manifestations in three spheres of dysfunction:
(1) those consequent to the accumulation of toxins that normally undergo renal excretion, including products of protein metabolism;
(2) those consequent to the loss of other renal functions, such as fluid and electrolyte homeostasis and hormone regulation; and
(3) progressive systemic inflammation and its vascular and nutritional
consequences.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Hyponatremia is not commonly seen in CKD patients but, when present, can respond to water restriction.
If the patient has evidence of ECFV expansion (peripheral edema, sometimes hypertension poorly responsive to therapy), he or she should be counseled regarding salt restriction.
Thiazide diuretics have limited utility in stages 3â5 CKD, such that administration of loop diuretics, including furosemide, bumetanide, or torsemide, may also be needed.
Resistance to loop diuretics in renal failure often mandates use of higher doses than those used in patients with near-normal kidney
function.
The combination of loop diuretics with metolazone, which inhibits the sodium chloride co-transporter of the distal convoluted tubule, can help effect renal salt excretion.
Ongoing diuretic resistance with intractable edema and hypertension in advanced CKD may serve as an indication to initiate dialysis.
These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis.
In addition, a host of medications can inhibit renal potassium excretion.
The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
Nonselective beta blockers may result in a
postprandial rise in the serum potassium
but do not cause persistent hyperkalemia.
These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis.
In addition, a host of medications can inhibit renal potassium excretion.
The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis.
In addition, a host of medications can inhibit renal potassium excretion.
The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
These include increased dietary potassium intake, protein catabolism, hemolysis, hemorrhage, transfusion of stored red blood cells, and metabolic acidosis.
In addition, a host of medications can inhibit renal potassium excretion.
The most important medications in this respect include the angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and spironolactone and other potassium-sparing diuretics such as amiloride, eplerenone, and triamterene.
Hypokalemia is not common in CKD and usually reflects markedly reduced dietary potassium intake, especially in association with excessive diuretic therapy or concurrent GI losses.
Hypokalemia can also occur as a result of primary renal potassium wasting in association with other solute transport abnormalities, such as Fanconiâs syndrome, renal tubular acidosis, or other forms of hereditary or acquired tubulointerstitial disease.
However, even with these conditions, as the GFR declines, the tendency to hypokalemia diminishes and hyperkalemia may supervene.
Therefore, the use of potassium supplements and potassium-sparing diuretics should be constantly
reevaluated as GFR declines.
Fanconi syndrome (also known as Fanconi&apos;s syndrome) is a disease of the proximal renal tubules[1] of the kidney in which glucose, amino acids, uric acid, phosphateand bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid after it is filtered through the glomerulus. It may be inherited, or caused by drugs or heavy metals.
Hyperkalemia, if present, further depresses ammonia production.
The combination of hyperkalemia and hyperchloremic metabolic acidosis is often present, even at earlier stages of CKD (stages 1â3), in patients with diabetic nephropathy or in those with predominant tubulointerstitial disease or obstructive uropathy; this is a non-anion-gap metabolic acidosis.
Treatment of hyperkalemia may increase renal ammonia production, improve renal generation of bicarbonate, and improve the metabolic acidosis.
Alkali supplementation may attenuate the catabolic state and possibly slow CKD progression and accordingly is recommended when the serum bicarbonate concentration falls below 20â23 mmol/L.
The concomitant sodium load mandates careful attention to volume status and the potential need for diuretic agents.
Water restriction is indicated only if there is a problem with hyponatremia.
Otherwise, patients with CKD and an intact thirst mechanism may be instructed to drink fluids in a quantity that keeps
them just ahead of their thirst.
Hyperkalemia often responds to dietary restriction of potassium, avoidance of potassium supplements (including occult sources, such as dietary salt substitutes) as well as potassium-retaining medications (especially ACE inhibitors or ARBs), or the use of kaliuretic diuretics.
Kaliuretic diuretics promote urinary potassium excretion, while potassium-binding resins, such as calcium resonium or sodium polystyrene, can promote potassium loss through the GI tract and may reduce the incidence of hyperkalemia in CKD patients.
Intractable hyperkalemia is an indication (although uncommon) to consider institution of dialysis in a CKD patient.
In most patients with stable CKD, the total-body content of sodium and water is modestly increased, although this may not be apparent on clinical examination.
Normal renal function guarantees that the tubular reabsorption of filtered sodium and water is adjusted so that urinary excretion matches intake.
Many forms of renal disease (e.g., glomerulonephritis) disrupt this glomerulotubular balance such that dietary intake of sodium exceeds its urinary excretion, leading to sodium retention and attendant extracellular fluid volume (ECFV) expansion.
This expansion may contribute to hypertension, which itself can accelerate the nephron injury.
As long as water intake does not exceed the capacity for water clearance, the ECFV expansion will be isotonic and the patient will have a normal plasma sodium
concentration and effective osmolality
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
renal osteodystrophy
CKD-MBD, thus defined, is characterized by the following:
âAbnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism
âAbnormalities in bone turnover, mineralization, volume linear growth, or strength
âVascular or other soft-tissue calcification
Sexual dysfunction â Significant abnormalities in sexual and reproductive function are frequently observed in patients with advanced renal disease. As an example, &gt;50 percent of uremic men complain of symptoms that include erectile dysfunction, decreased libido, and marked declines in the frequency of intercourse ;
in addition, disturbances in menstruation and fertility are commonly encountered in women with CKD, usually leading to amenorrhea by the time the patient reaches ESRD. An important clinical implication of these abnormalities is that pregnancy that is carried to term is uncommon in women with a plasma creatinine concentration of âĽ3 mg/dL (265 micromol/L)
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
renal osteodystrophy
CKD-MBD, thus defined, is characterized by the following:
âAbnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism
âAbnormalities in bone turnover, mineralization, volume linear growth, or strength
âVascular or other soft-tissue calcification
Calciphylaxis (calcific uremic arteriolopathy) is a devastating condition
seen almost exclusively in patients with advanced CKD. It
is heralded by livedo reticularis and advances to patches of ischemic
necrosis, especially on the legs, thighs, abdomen, and breasts
However, more recently, calciphylaxis has been seen with increasing frequency in the absence of severe
hyperparathyroidism.
one of the effects of warfarin therapy is to decrease the vitamin Kâdependent regeneration of matrix GLA protein.
This latter protein is important in preventing vascular calcification.
Thus, warfarin treatment is considered a risk factor for calciphylaxis, and if a patient develops this syndrome, this medication should be discontinued and replaced with alternative forms of anticoagulation.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
renal osteodystrophy
CKD-MBD, thus defined, is characterized by the following:
âAbnormalities of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D metabolism
âAbnormalities in bone turnover, mineralization, volume linear growth, or strength
âVascular or other soft-tissue calcification
.
The principal complications of abnormalities of calcium and
phosphate metabolism in CKD
occur in the skeleton and
the vascular bed,
with occasional severe involvement of extraosseous soft tissues.
The major disorders of bone disease can be classified into those associated with high bone turnover with increased PTH levels
(including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and low bone turnover with low or normal
PTH levels (adynamic bone disease and osteomalacia).
The principal complications of abnormalities of calcium and
phosphate metabolism in CKD
occur in the skeleton and
the vascular bed,
with occasional severe involvement of extraosseous soft tissues.
The major disorders of bone disease can be classified into those associated with high bone turnover with increased PTH levels
(including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism) and low bone turnover with low or normal
PTH levels (adynamic bone disease and osteomalacia).
Recent epidemiologic evidence has shown a strong association
between hyperphosphatemia and increased cardiovascular mortality
rate in patients with stage 5 CKD and even in patients with earlier
stages of CKD.
The magnitude of the calcification is proportional to age and hyperphosphatemia and is also associated
with low PTH levels and low bone turnover.
It is possible that in
patients with advanced kidney disease, ingested calcium cannot be
deposited in bones with low turnover and, therefore, is deposited
at extraosseous sites, such as the vascular bed and soft tissues.
It is interesting in this regard that there is also an association between
osteoporosis and vascular calcification in the general population.
Finally, there is recent evidence indicating that hyperphosphatemia
can induce a change in gene expression in vascular cells to an
osteoblast-like profile, leading to vascular calcification and even
ossification.
The dialysis disequilibrium syndrome (DDS) is an increasingly rare syndrome characterized by neurologic symptoms of varying severity that affect dialysis patients, particularly when they are first started on hemodialysis [1,2]. It is thought to be due primarily to cerebral edema.
Risk factors for DDS include the following [2-6]:
âFirst dialysis treatment
âMarkedly elevated blood urea concentration predialysis (ie, &gt;175 mg/dL or 60 mmol/L)
âChronic kidney disease (CKD, as compared with acute kidney injury [AKI])
âSevere metabolic acidosis
âOlder age
âPediatric patients
âPre-existing neurologic disease (head trauma, stroke, seizure disorder)
âOther conditions characterized by cerebral edema (hyponatremia, hepatic encephalopathy, malignant hypertension)
âAny condition that increases permeability of the blood brain barrier (such as sepsis, vasculitis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome [TTP/HUS], encephalitis, or meningitis)
Reverse osmotic shift â Hemodialysis rapidly removes small solutes such as urea, particularly in patients who have marked azotemia. The reduction in blood urea nitrogen (BUN) lowers the plasma osmolality, thereby creating a transient osmotic gradient that promotes water movement into the cells. In the brain, this water shift produces cerebral edema and a variable degree of acute neurologic dysfunction.
The pathogenetic importance of urea in DDS has been demonstrated by experiments in uremic rats [10-12]. In one report, for example, rapid dialysis lowered the BUN from 200 to 95 mg/dL (72 to 34 mmol/L) in 90 minutes [10]. This change was associated with a 6 percent increase in brain water. Neither undialyzed rats nor those rats dialyzed against a bath to which urea was added to prevent a fall in BUN developed cerebral edema. Furthermore, the retention of brain urea appears to account for most of the increase in brain water [11].
Urea is generally considered an &quot;ineffective&quot; osmole because of its ability to permeate cell membranes. However, this effect may take several hours to reach completion. Thus, there is insufficient time for urea equilibration when hemodialysis rapidly reduces the BUN; as a result, urea transiently acts as an effective osmole, promoting water movement into the brain. In the above experiments, for example, the 53 percent acute reduction in BUN was only associated with a 13 percent reduction in brain urea nitrogen [10]. In addition, animal studies have suggested that there may be a decrease in urea transporters and an increase in water channels in uremia, which would increase the reflection coefficient (or ability to elicit an osmotic force) of urea [13].
Intracerebral acidosis and idiogenic osmoles â Some investigators have suggested that the reverse osmotic shift cannot account for the development of cerebral edema in DDS, since urea movement out of the brain is sufficiently rapid to prevent a large osmotic gradient between the brain and extracellular fluid [2]. They have proposed that a decrease in cerebral intracellular pH, occurring via an uncertain mechanism, is of primary importance [2,12]. Both displacement of bound sodium and potassium by the excess hydrogen ions and enhanced production of organic acids can increase intracellular osmolality and promote water movement into the brain [14].
PREVENTION â Measures to prevent DDS should be used among patients at high risk, particularly including new dialysis patients, patients who have extremely high blood urea nitrogen (BUN) concentrations, or patients who have other active neurologic conditions at the time of dialysis. The most important preventive measure is to limit the reduction in BUN per treatment so that there is a gradual reduction that is distributed over several days.
Slow urea removal can be achieved by one of the following methods:
âWith hemodialysis, therapy can be initiated with two hours of dialysis at a relatively low blood flow rate of 150 to 250 mL/min with a small surface area dialyzer (0.9 to 1.2 m2).
âThe patient should have a repeat dialysis session daily for three to four days, with modifications in the prescription depending upon clinical response. If the patient shows no signs of DDS, the blood flow rate can be increased by 50 mL/min per treatment (up to 300 to 400 mL/min), and the duration of dialysis can be increased in 30-minute increments (up to four or more hours, as necessary for adequate solute removal).
âPatients who also have marked fluid overload can be treated with ultrafiltration (which removes less urea per unit time and does not change plasma osmolarity), followed by a short period of hemodialysis [15]. (See &quot;Renal replacement therapy (dialysis) in acute kidney injury (acute renal failure): Metabolic and hemodynamic considerations&quot;.)
âAmong patients with extremely elevated BUN or neurologic symptoms, dialysis should be initiated as an inpatient, although there are no data that have demonstrated better outcomes with this approach
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
The CKD-related risk factors comprise anemia, hyperphosphatemia,
hyperparathyroidism, sleep apnea, and generalized inflammation.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
Virtually all abnormalities in this table are completely reversed in time by successful renal transplantation.
The response of these abnormalities to hemodialysis or peritoneal dialysis therapy is more variable.
(I) denotes an abnormality that usually improves with an optimal program of dialysis and related therapy;
(P) denotes an abnormality that tends
to persist or even progress, despite an optimal program;
(D) denotes an abnormality that develops only after initiation of dialysis therapy.
bImproves with dialysis and erythropoietin therapy.
Abbreviation: Lp(a), lipoprotein A.
A normocytic, normochromic anemia is observed as early as stage
3 CKD and is almost universal by stage 4. The primary cause in
patients with CKD is insufficient production of erythropoietin
(EPO) by the diseased kidneys.
A normocytic, normochromic anemia is observed as early as stage
3 CKD and is almost universal by stage 4. The primary cause in
patients with CKD is insufficient production of erythropoietin
(EPO) by the diseased kidneys.
A normocytic, normochromic anemia is observed as early as stage
3 CKD and is almost universal by stage 4. The primary cause in
patients with CKD is insufficient production of erythropoietin
(EPO) by the diseased kidneys.
Goal Hgb 11-12
Recombinant erythropoeitin
Epogen/Procrit 50-150 U/kg/wk SQ
Darbopoetin alfa (ARANESP) Start 0.45mcg/kg SQ once every 2 weeks, usually dosed every three to four weeks when patient is stable in the therapeutic range
Recent concerns re increased risk of cardiovascular events associated with an elevated Hgb in association with use of high doses of these products
Iron
Goal Ferritin &gt;200, TSAT &gt;20%
Oral agents
Chromagen: 33% iron
Ferrous sulfate: 20% iron
Niferex (Polysaccharide with Vit C): 150mg elemental iron
Ferrous fumurate: 33% iron
Ferrous gluconate (Fergon): 12% iron
Oral agents do not work well, primarily b/o ill tolerated GI side effects
A normocytic, normochromic anemia is observed as early as stage
3 CKD and is almost universal by stage 4. The primary cause in
patients with CKD is insufficient production of erythropoietin
(EPO) by the diseased kidneys.
A number of different modalities can be used in this setting, including the correction of anemia, the administration of desmopressin (dDAVP), cryoprecipitate, estrogen, and the initiation of dialysis.
Abnormal bleeding time and coagulopathy in patients with
renal failure may be reversed temporarily with desmopressin
(DDAVP), cryoprecipitate, IV conjugated estrogens, blood
transfusions, and EPO therapy. Optimal dialysis will usually
correct a prolonged bleeding time.
A normocytic, normochromic anemia is observed as early as stage
3 CKD and is almost universal by stage 4. The primary cause in
patients with CKD is insufficient production of erythropoietin
(EPO) by the diseased kidneys.
Limited data suggest that lipid lowering may have an additional benefit in patients with CKD, which is slowing the rate of progression of the underlying renal disease.
.
.
. Similar patterns relating to late referral have been reported from other parts of the world [69-71]. The proportion of dialysis patients who required dialysis within one month of the first visit to a nephrologist ranged from 25 percent in Paris, France [69] to 58 percent in Sao Paulo, Brazil [70]. The prevalence of late referral can also have significant regional variation within a country; in the larger cities of Australia, the proportion of patients referred within three months of needing to start dialysis ranged from 14 to 44 percent [72].
Causes of late referral â Late referral to the nephrologist can be due to unavoidable causes, the referral biases of physicians, patient factors, socioeconomic status of the patient, and/or the structure of the healthcare system(s) within a certain country .
Unavoidable causes â Unavoidable causes of late referral include end-stage renal disease (ESRD) that follows acute kidney injury (AKI), &quot;asymptomatic&quot; kidney failure only presenting at an advanced stage, or a patient&apos;s refusal to seek help until symptoms occur.
The majority of patients referred to the nephrologist in a timely manner tend to have a functioning permanent access at the start of dialysis compared with only a small minority of late referrals
The late referral of patients has therefore resulted in a large number of dialysis patients without permanent vascular access at the time of initiation of dialysis
. Multidisciplinary chronic kidney disease clinic â The optimal medical care of CKD patients may be best provided by a team of healthcare professionals who practice at a single site (ie, a CKD clinic), following the principles of the chronic disease model of care [100]. Such CKD clinics focus on guideline-driven nephrology care, management of comorbidities, lifestyle modification, and patient education in order to optimize patient outcomes. Observational and nonrandomized prospective studies have suggested that, compared with standard nephrology care, patients who attend a multidisciplinary CKD clinic have fewer hospitalizations, are more likely to have an arterial-venous fistula rather than graft or catheter, are more likely to start dialysis as an outpatient, and are more likely to adhere to established CKD anemia or mineral and bone disease (MBD) goals
. Multidisciplinary chronic kidney disease clinic â The optimal medical care of CKD patients may be best provided by a team of healthcare professionals who practice at a single site (ie, a CKD clinic), following the principles of the chronic disease model of care [100]. Such CKD clinics focus on guideline-driven nephrology care, management of comorbidities, lifestyle modification, and patient education in order to optimize patient outcomes. Observational and nonrandomized prospective studies have suggested that, compared with standard nephrology care, patients who attend a multidisciplinary CKD clinic have fewer hospitalizations, are more likely to have an arterial-venous fistula rather than graft or catheter, are more likely to start dialysis as an outpatient, and are more likely to adhere to established CKD anemia or mineral and bone disease (MBD) goals