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MGR REVIEW
PROF 임천규 / R3 김다래
MGR REVIEW
1. DM nephropathy의 진단기준 - 이 증례에서의 해당 사항
2. DM의 chronic complications - 이 증례에서의 해당 사항
3. 이 환자에서 최근의 급격한 sCr과 K 상승
1) target BP?
2) ARB의 사용 및 용량 증량의 문제점?
이를 2013 ESH/ESC guidelines & 2014 JNC VIII guideline 비교
4. DM CKD 환자에서 cardiovascular complication을 예방 및 치료하
기 위해서 함께 투여해야 할 약제와 기타 다른 management (식사)
5. 이 환자에서의 단백뇨 치료 어려움?
6. 적절한 투석 시작 시기?
7. 이 환자와 같이 투석 전 단계나 투석 환자에서의 혈당조절 위한 경
구혈당강하제 및 인슐린 치료시 주의할 점
1. DM nephropathy의 진단기준
Patients with diabetes should be screened annually for DKD
- Initial screening should commence:
- 5 years after the diagnosis of type 1 diabetes (A)
- from diagnosis of type 2 diabetes (B)
Screening should include:
• Measurements of urinary ACR in a spot urine sample (B)
• Measurement of serum creatinine and estimation of GFR (B)
In most patients with diabetes, CKD should be attributable to diabetes if:
•
Macroalbuminuria(ACR>300mg/g) is present (B)
•
Microalbuminuria(ACR 30-300mg/g) is present
– in the presence of diabetic retinopathy (B)
– in type 1 diabetes of at least 10 years' duration (A)
(NKF-KDOQI guidelines, Am J Kidney Dis, 49, Suppl 2, S1-S180, 2007)
1. DM nephropathy의 진단기준
The 2007 KDOQI Guidelines for diabetes and chronic kidney disease
• CKD : diabetic nephropathies in most DM patients
if (1)albuminuria and (2)diabetic retinopathy are both present
• if diabetic retinopathy is absent → other causes of CKD ?
•
Albuminuria in DM is occasionally due to a non-diabetic glomerular
disease other than diabetic nephropathy.
– absence of diabetic retinopathy
– acute onset of renal disease
– presence of an active urine sediment (red cells, cellular casts)
– signs and symptoms of another systemic disease
– significant reduction in the GFR (>30%) within 2-3 months of the
administration of ACE inhibitors or ARBs
(NKF-KDOQI guidelines, Am J Kidney Dis, 49, Suppl 2, S1-S180, 2007)
Diagnosis of diabetic nephropathy
(NKF-KDOQI guidelines, Am J Kidney Dis, 49, Suppl 2, S1-S180, 2007)
1. DM nephropathy의 진단기준
2012.11.07 Urine chemistry
2012.06.04 Urinalysis
-
Urine Protein
690 mg/dL
Bilirubin
-
Urine Creatinine
79 mg/dL
Urobilinogen (mg/dL)
-
Urine PCR
Keton
-
Urinalysis Occult Blood
Protein (mg/dL)
Nitrite
8.73
Proteinuria(+)
+++(300)
-
2012.06.03 chemistry
++++(1000)
BUN/Cr (mg/dL)
27/2.1
Ph
5.5
Na/K/Cl (mmol/L)
138/4.1/99
SG
1.023
Glucose (mg/dL)
Leukocytes
Urine Micro RBC (HPF)
WBC (HPF)
eGFR
2~4
0~1
Hematuria(-)
35.24
2012.11.07 AP sono + Renal doppler sono
9.6cm
Both kidney main renal arteries, veins
: patency intract
no artery stenosis
no anatomical abnormality
10.6cm
2012.06.03 Fundoscopy
1) Rt. Eye
2) Lt. Eye
moderate non-proliferative DM retinopathy
Cataract
Diabetic nephropathy
(CKD stage 3)
2. DM의 chronic complications
Microvascular
Macrovascular
Retinopathy
Cerebrovascular
disease
Nephropathy
Coronary
heart
disease
Neuropathy
Peripheral
vascular
disease
(UK Prospective Diabetes Study Group. UKPDS 33. Lancet. 1998;352:837-853)
3. Hyperkalemia in DM CKD
3. Hyperkalemia in DM CKD
EKG : NSR
serum K : 6.0
urine K
: 28
urine Na
: 49
TTKG : 8.53
+ ARB 증량
eGFR : 6.18
CKD stage 5
3. Hyperkalemia in DM CKD
N Engl J Med 2004; 351:585-592, August 5, 2004
3. Hyperkalemia in DM CKD
•
•
•
•
ACE inhibitors and ARBs
– treat HTN
– decrease cardiovascular events in high-risk patients
– A side effect of such therapy is development of hyperkalemia
Hyperkalemia develops in approximately 10 percent of outpatients
within a year after these drugs are prescribed
Patients at greatest risk for hyperkalemia
– diabetes mellitus
– impaired renal function in whom a defect in the excretion of renal
potassium
Hyperkalemia is an uncommon complication of therapy with ACE
inhibitors or ARBs in patients without risk factors
N Engl J Med 2004; 351:585-592, August 5, 2004
•
ACE inhibitors and ARBs
– therapeutic dilemma due to development of hyperkalemia
– these medications may be of benefit in slowing the progression of
chronic kidney disease
– since the patients at highest risk for this complication are the same
patients who derive the greatest cardiovascular benefit from these
drugs
실제로
임상에서는?
N Engl J Med 2004; 351:585-592, August 5, 2004
2014 Guideline for Management of High Blood Pressure, JAMA. 2014;311(5):507-520.
[CONCLUSION]
Use of an ACEI or an ARB will commonly increase serum creatinine and may produce other
metabolic effects such as hyperkalemia, particularly in patients with decreased kidney
function. Although an increase in creatinine or potassium level does not always require
adjusting medication, use of renin-angiotensin system inhibitors in the CKD population
requires monitoring of electrolyte and serum creatinine levels, and in some cases, may
require reduction in dose or discontinuation for safety reasons.
2013 ESH/ESC Guidelines for the management of arterial hypertension
Journal of Hypertension, Volume 31, Number 7, July 2013
6.9.1 Summary of recommendations on therapeutic
strategies in hypertensive patients with nephropathy
Journal of Hypertension, Volume 31, Number 7, July 2013
4. DM CKD - Cardiovascular complication
ESC guidelines European Heart Journal August 30, 2013
4. DM CKD - Cardiovascular complication
1. Insulin resistance
2. Endothelial dysfunction
oxidative stress
vascular inflammation
3. Macrophage dysfunction
4. Atherogenic dyslipidemia
5. Coagulation and platelet function
ESC guidelines European Heart Journal August 30, 2013
4. DM CKD - Cardiovascular complication
ESC guidelines European Heart Journal August 30, 2013
5. 이 환자에서의 단백뇨 치료 어려움?
6. 적절한 투석 시작 시기?
• There are no absolute levels of kidney function that
indicate a requirement for dialysis !
6. 적절한 투석 시작 시기?
• Clinical indications to initiate dialysis
Life threatening!
1. Pericarditis or Pleuritis
2. Progressive uremic encephalopathy
3. Neuropathy with signs such as confusion, asterixis, myoclonus, wrist or
foot drop, in severe cases, seizures
4.
5.
6.
7.
Uremic bleeding
Fluid overload refractory to diuretics
Hypertension poorly responsive to antihypertensive medication
Persistent metabolic disturbances that are refractory to medical
therapy; hyperkalemia, metabolic acidosis, hypercalcemia,
hypocalcemia, and hyperphosphatemia
8.
Persistent nausea and vomiting
6. 적절한 투석 시작 시기?
•
•
•
There is conflicting evidence concerning the effect of the early
initiation of dialysis on survival
symptoms and signs of uremia → clinicians and patients
Initiation of dialysis : (1)clinical factors + (2)the estimated GFR
uremic Sx, signs
•
•
extremely low eGFR
The initiation of dialysis should be considered in the asymptomatic
patient with an extremely low GFR, such as an estimated GFR of
approximately 8-10mL/min/1.73m2.
However, some clinicians may choose to closely monitor asymptomatic
patients with progressive CKD even when GFR is below this level, with
the initiation of dialysis upon the onset of uremic signs/symptoms.
이 환자에게서의
적절한 투석 시작 시기는 ?
7. DM CKD 환자에서의 혈당조절
KDOQI Diabetes Guideline: 2012 Update Am J Kidney Dis. 2012;60(5):850-886
Guideline 2: Management of Hyperglycemia
and General Diabetes Care in CKD
•
•
•
•
Hyperglycemia : fundamental cause of vascular target organ
complications, including diabetic kidney disease.
Intensive treatment of hyperglycemia prevents elevated albuminuria or
delays its progression
But, patients treated by approaches designed to achieve near normal
glycemia may be at increased risk of severe hypoglycemia.
Evidence that intensive treatment has an effect on loss of GFR is sparse :
즉, 증거가 부족하다!
2.1: We recommend a target HbA1c of 7.0% to prevent or delay
progression of the microvascular complications of diabetes(DKD). (1A)
2.2: We recommend not treating to an HbA1c target of <7.0% in patients
at risk of hypoglycemia. (1B)
2.3: We suggest that target HbA1c be extended above 7.0% in individuals
with co-morbidities or limited life expectancy and risk of hypoglycemia. (2C)
KDOQI Diabetes Guideline: 2012 Update Am J Kidney Dis. 2012;60(5):850-886
Paradigm shift (ADA 2012)
The lower is
the better
Individualized
therapy
Patient attitude
Hypoglycemia risk
Disease duration
Life expectancy
Comorbidities
Established vascular complications
(ADA & ESAD position statement, Diabetes Care, 35: 1364-1379, 2012)
7. DM CKD 환자에서의 혈당조절
KDOQI Diabetes Guideline: 2012 Update Am J Kidney Dis. 2012;60(5):850-886
7. DM CKD 환자에서의 혈당조절
실제 임상에서
metformin을 중단하는 경우?
KDOQI Diabetes Guideline: 2012 Update Am J Kidney Dis. 2012;60(5):850-886
경청해주셔서 감사합니다