1. CKD Treatment 순천향 대학교병원 신장내과 R3 김재연

2. Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function, and a progressive decline in glomerular filtration rate (GFR).

3. Pathophysiology The pathophysiology of CKD involves two broad sets of mechanisms of damage: (1)Initiating mechanisms specific to the underlying etiology (e.g., immune complexes and mediators of inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium (2)A set of progressive mechanisms -> Involving hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology. -> The responses to reduction in nephron number are mediated by vasoactive hormones, cytokines, and growth factors.

4. 만성 신부전 환자에서 골대사와 골질환 만성 신부전 환자에서 빈혈 관리 Protein restriction

5. 만성 신장에서 골대사와 골질환

6. Bone Manifestations of CKD The major disorders of bone disease can be classified -High bone turnover with increased PTH levels (including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism) -Low bone turnover with low or normal PTH levels (adynamic bone disease and osteomalacia)

7. The pathophysiology of secondary hyperparathyroidism and the consequent high-turnover bone disease is related to abnormal mineral metabolism through the following events: (1) Declining GFR leads to reduced excretion of phosphate, and, thus phosphate retention (2) The retained phosphate stimulates increased synthesis of PTH and growth of parathyroid gland mass (3) Decreased levels of ionized calcium, resulting from diminished calcitriol production by the failing kidney as well as phosphate retention, also stimulate PTH production. Low calcitriol levels contribute to hyperparathyroidism, both by leading to hypocalcemia and also by a direct effect on PTH gene transcription.

8. Bone Manifestations of CKD In addition to increased production of PTH from the parathyroid cells, the mass of parathyroid glands increases progressively with CKD. The cell mass may assume one of the following growth patterns: (1) Diffuse hyperplasia (polyclonal) (2) Nodular growth (monoclonal) within diffuse hyperplasia (3) Diffuse monoclonal hyperplasia ("adenoma" or tertiary autonomous hyperparathyroidism).

9. The hyperparathyroidism stimulates bone turnover and leads to osteitis fibrosa cystica. Clinical manifestations of severe hyperparathyroidism include - bone pain and fragility - the brown tumors, rare compression syndromes caused by brown tumors - erythropoietin resistance in part related to the bone marrow fibrosis Furthermore, PTH is a uremic toxin, and high levels are associated with muscle weakness, fibrosis of cardiac muscle, and nonspecific constitutional symptoms.

10. Bone Manifestations of CKD Low-turnover bone disease can be grouped into two categories— adynamic bone disease and osteomalacia. In the latter condition, there is accumulation of unmineralized bone matrix that may be caused by vitamin D deficiency, excess aluminum deposition, or even metabolic acidosis. Adynamic bone disease is increasing in prevalence, especially among diabetics and the elderly. It is characterized by reduced bone volume and mineralization and may result from excessive suppression of PTH production.

11. EVALUATION OF CALCIUM AND PHOSPHORUS METABOLISM

13. ASSESSMENT OF BONE DISEASE ASSOCIATEDWITH CKD

15. EVALUATION OF SERUM PHOSPHORUS LEVELS

16. RESTRICTION OF DIETARY PHOSPHORUS IN PATIENTSWITH CKD

19. USE OF PHOSPHATE BINDERS IN CKD

22. SERUM CALCIUM AND CALCIUM-PHOSPHORUS PRODUCT CKD stage 3,4,5 의 serum calcium level 은 normal range 를 유지 (Lower end 유지,8.4~9.5) Calcium >10.2 -> binder, Vit D 투여 중이라면 dose reduction 시행 하고, effect 없다 면 low dialysis calcium 을 이용한 투석을 3-4 주 정도 apply Calcium intake 2000 mg/day 를 넘기지 않는다. Calcium < 8.4 -> Sx. (Parathesia, Troisseau's sign, bronchospasm, laryngospasm, tetany, seizure) 있으면 calcium 보충. PTH level 이 stage 에 따른 target 보다 높다면 보충해준다.

24. PREVENTION AND TREATMENT OF VITAMIN D INSUFFICIENCY AND VITAMIN D, DEFICIENCY IN CKD PATIENTS 1. CKD Stage 3,4 에서 iPTH level 이 target range 보다 높다면 Vit.D 측정, 정상 이라면 anually. -> 25-hydroxyvitamin D < 30 ng/ml 이면, vitamin D2(ergocalciferol) start (opinion) 2. Correction Calcium,P every 3month check 3. Corrected Calcium 10.2 를 넘으면, ergocalciferol 등 hold 한다. 4. P >4.6 넘으면 phosphate binder 추가하고, 교정 되지 않는다면 Vit.D D/C 5. CKD stage 5 환자 에서는 PTH 가 300 을 넘는다면 active vitamin D sterol 사용한다. (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol)

27. 만성 신부전 환자에서 빈혈 관리

28. Anemia 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, insufficient production of erythropoietin (EPO) by the diseased kidneys. Additional factors include iron deficiency, acute and chronic inflammation with impaired iron utilization ("anemia of chronic disease"), severe hyperparathyroidism with consequent bone marrow fibrosis, and shortened red cell survival in the uremic environment. Less common causes include folate and vitamin B12 deficiency and aluminum toxicity. In addition, comorbid conditions such as hemoglobinopathy can worsen the anemia

30. IDENTIFYING PATIENTS AND INITIATING EVALUATION

32. EVALUATION OF ANEMIA IN CKD

33. Hb RANGE

34. USING ESAs

35. USING IRON AGENTS

36. USING PHARMACOLOGICAL AND NONPHARMACOLOGICAL ADJUVANTS TO ESA TREATMENT IN HD-CKD

37. Protein Restriction While protein restriction has been advocated to -> reduce symptoms associated with uremia, -> it may also slow the rate of renal decline at earlier stages of renal disease. A number of studies have shown that protein restriction may be effective in slowing the progression of CKD, especially proteinuric and diabetic renal diseases.

38. Protein Restriction However, the Modification of Diet in Renal Disease study was unable to demonstrate a robust benefit in delaying progression to advanced stages of CKD with dietary restriction of protein intake.

39. Nonetheless, restriction of dietary protein intake has been recommended for CKD patients. KDOQI clinical practice guidelines include a daily protein intake of between 0.60 and 0.75 g/kg per day depending upon patient adherence, comorbid disease, presence of proteinuria, and nutritional status. It is further advised that at least 50% of the protein intake be of high biologic value. As patients approach stage 5 CKD, spontaneous protein intake tends to decrease, and patients may enter a state of protein-energy malnutrition. In these circumstances, a protein intake of up to 0.90 g/kg per day might be recommended, again, with an emphasis on proteins of high biologic value.

40. Protein Restriction Sufficient energy intake is important to prevent protein-calorie malnutrition, and 35 kcal/kg is recommended. Monitoring of parameters of nutritional status must accompany the dietary intervention, using the parameters outlined above in the section on GI and nutritional abnormalities.

41. Evaluation of Protein-Energy Nutritional Status