17 CKD Hanif diagnosis and treatmentpptx

Chronic Kidney Disease diagnosis and treatment

1. Chronic Kidney Disease Definiations Pathogenesis Causes Clinical feaures Diagnosis Complications treatment

2. Definitations CKD is defined by the presence of kidney damage  or  decreased kidney function  for three or more months , irrespective of the cause persistence of the damage or decreased function for at least three months is  necessary  to distinguish CKD from acute kidney disease.

3. Kidney damage refers to pathologic abnormalities, whether established via kidney 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

4. end-stage renal disease or stage 5 CKD represents a stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys leads to death unless the toxins are removed by renal replacement therapy, using dialysis or kidney transplantation

5. Pathogenesis two broad sets of mechanisms of damage : I nitiating mechanisms specific to the underlying etiology (e.g ., abnormalities in kidney development or integrity, immune complex deposition and inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium ) H yperfiltration and hypertrophy of the remaining viable nephrons , that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology and lead to further decline in kidney function

6. CKD Risk Factors small for gestation birth weight Childhood obesity Hypertension D iabetes mellitus autoimmune disease advanced age African ancestry a family history of kidney disease a previous episode of acute kidney injury presence of proteinuria abnormal urinary sediment Structural abnormalities of the urinary tract

7. Malignancy Family History Infections like Hep C and HIV Nephrotoxics like NSAID Metabolic Syndromes Cardiovascular disease Autosomal Dominant Polycytsic Kideny disease

8. CKD Risk Factors* Modifiable Diabetes Hypertension History of AKI Frequent NSAID use Non-Modifiable Family history of kidney disease, diabetes, or hypertension Age 60 or older (GFR declines normally with age) Race/U.S. ethnic minority status *Partial list AKI, acute kidney injury

9. ESRD, end stage renal disease USRDS ADR, 2007 Diabetes and hypertension are leading causes of kidney failure Incident ESRD rates, by primary diagnosis, adjusted for age, gender, & race.

10. CKD as a Public Health Issue 26 million American affected Prevalence is 11-13% of adult population in the US 28 % of Medicare budget in 2013, up from 6.9% in 1993 $42 billion in 2013 Increases risk for all-cause mortality, CV mortality, kidney failure (ESRD), and other adverse outcomes. 6 fold increase in mortality rate with DM + CKD Disproportionately affects African Americans and Hispanics NKF Fact Sheets . http :// www.kidney.org/news/newsroom/factsheets/FastFacts . Accessed Nov 5, 2014. USRDS. www.usrds.org . Accessed Nov 5, 2014. Coresh et al . JAMA . 2007. 298:2038-2047. ESRD, end stage renal disease

11. Leading Causes of CKD

12. Causes of CKD

13. Criteria for CKD Abnormalities of kidney structure or function, present for >3 months , with implications for health Either of the following must be present for >3 months: ACR >30 mg/g Markers of kidney damage (one or more*) GFR <60 mL/min/1.73 m 2 *Markers of kidney damage can include nephrotic syndrome , nephritic syndrome, tubular syndromes, urinary tract symptoms, asymptomatic urinalysis abnormalities , asymptomatic radiologic abnormalities , hypertension due to kidney disease. m²

14. Old Classification of CKD as Defined by Kidney Disease Outcomes Quality Initiative (KDOQI) Modified and Endorsed by KDIGO Note: GFR is given in mL/min/1.73 2 m² National Kidney Foundation. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis 2002;39( suppl 1):S1-S266 Stage Description Classification by Severity Classification by Treatment 1 Kidney damage with normal or increased GFR GFR ≥ 90 2 Kidney damage with mild decrease in GFR GFR of 60-89 T if kidney transplant 3 Moderate decrease in GFR GFR of 30-59 recipient 4 Severe decrease in GFR GFR of 15-29 D if dialysis 5 Kidney failure GFR < 15 D if dialysis KDIGO, Kidney Disease: Increasing Global Outcomes

15. Classification of CKD Based on GFR and Albuminuria Categories: “Heat Map”

16. Calculations Cockcroft-Gault Men: CrCl (mL/min) = (140 - age) x wt (kg) SCr x 0.81 Women: multiply by 0.85 MDRD GFR (mL/min per 1.73 m 2 ) = 186 x (SCr x 0.0113) -1.154 x (age) -0.203 x (0.742 if female) x (1.12 if African-American)

17. Signs & Symptoms General Fatigue & malaise Edema Ophthalmologic AV nicking Cardiac HTN Heart failure Pericarditis CAD GI Anorexia Nausea/vomiting Dysgeusia Skin Pruritis Pallor Neurological MS changes Seizures

18. Clinical Manifestations Stages 1–4 CKD are asymptomatic. Symptoms develop slowly with the progressive decline in GFR, are nonspecific, and do not manifest until kidney disease is far advanced (GFR less than 5–10 mL/min/1.73 m2). Uremic syndrome . Fatigue anorexia, nausea a metallic taste in the mouth.

19. Neurologic symptoms such as irritability, memory impairment, insomnia, restless legs, paresthesias , and twitching may be due to uremia. Generalized pruritus (without rash) decreased libido and menstrual irregularities Pericarditis Pleuritic chest pain

20. Common physical findings Hypertension volume overload. Uremic signs: seen with a profound decrease in GFR (less than 5–10 mL/min/1.73 m2 ) generally sallow and ill appearance halitosis (uremic fetor) the uremic encepholopathic signs of decreased mental status, asterixis , myoclonus, and possibly seizures

21. Asterixis , Flapping Tremor

22. Lab Findings abnormal GFR persisting for at least 3 months. Persistent proteinuria or abnormalities renal imaging ( eg , polycystic kidneys or a single kidney) are also diagnostic of CKD, even when eGFR is normal Anemia, hyperphosphatemia, hypocalcemia, hyperkalemia, and metabolic acidosis

23. urinary sediment: show broad waxy casts dilated,hypertrophic nephrons. Proteinuria may be present . Quantification of urinary protein is important for several reasons . First , it helps narrow the differential diagnosis of the etiology of the CKD Second, the presence of proteinuria is associated with more rapid progression of CKD and with increased risk of cardiovascular mortality

24. Imaging small , echogenic kidneys bilaterally (less than 9–10 cm) by ultrasonography suggests the chronic scarring of advanced CKD.

25. Large kidneys: adult polycystic kidney disease, diabetic nephropathy HIV associated nephropathy plasma cell myeloma amyloidosis Obstructive uropathy

26. Complications Cardiac Bone AND Minerals Hematologic Hyperkalemia Acid-base disorders Neurologic endocrine

27. Cardiac Complications HTN CAD HF Afib Pericarditis

28. HTN in CKD most common complication of CKD; progressive and salt-sensitive control of hypertension should focus on both pharmacologic and nonpharmacologic therapy ( eg , diet, exercise, weight loss , treatment of obstructive sleep apnea ) low salt diet (2 g/day ) Diuretics needed to control HTN Initial drug therapy for proteinuric patients should include ACE inhibitors or ARBs

29. HTN in CKD ACEi and ARB patients must have serum creatinine and potassium checked within 7–14 days. A rise in serum creatinine greater than 30 % from baseline mandates reduction or cessation of the drug should not be used in combination BP Goal 130/80

30. CAD higher risk for death from CVD than the general population. Traditional modifiable risk factors for CVD , such as hypertension, tobacco use, and hyperlipidemia, should be aggressively treated in patients with CKD . Uremic vascular calcification involving disordered phosphorus homeostasis and other mediators may also be a cardiovascular risk factor in these patients

31. Atrial Fibrillation 20% prevalence in patients receiving dialysis. Rate and rhythm management should be addressed.

32. Heart Failure due to hypertension, volume overload, and anemia accelerated rates of atherosclerosis and vascular calcification resulting in vessel stiffness LVH and HFpEF Diuretics and Salt Restriction ACE inhibitors and ARBs can be used for patients with advanced CKD with close monitoring of blood pressure as well as for hyperkalemia and worsening kidney function

33. Pericarditis uremic patients; typical Findings :pleuritic chest pain and a friction rub. significant pericardial effusion may result in pulsus paradoxus , an enlarged cardiac silhouette on chest radiograph, and low QRS voltage and electrical alternans on ECG . The effusion is generally hemorrhagic, and anticoagulants should be avoided if this diagnosis is suspected. Cardiac tamponade can occur; therefore, uremic pericarditis is a mandatory indication for hospitalization and initiation of hemodialysis

34. Disorders of Mineral Metabolism metabolic bone disease of CKD refers to the complex disturbances of calcium and phosphorus metabolism, parathyroid hormone (PTH), active vitamin D, and fibroblast growth factor-23 (FGF-23) homeostasis

35. typical pattern seen as early as CKD stage 3 is hyperphosphatemia , hypocalcemia, and hypovitaminosis D, resulting in secondary hyperparathyroidism

36. Bone disease, or renal osteodystrophy , in advanced CKD is common and there are several types of lesions. Renal osteodystrophy can be diagnosed only by bone biopsy, which is rarely done. The most common bone disease, osteitis fibrosa cystica , is a result of secondary hyperparathyroidism and th osteoclast stimulating effects of PTH high-turnover disease with bone resorption and subperiosteal lesions; it can result in bone pain and proximal muscle weakness

37. Adynamic bone disease, or low-bone turnover, is becoming more common ; it may result iatrogenically from suppression of PTH or via spontaneously low PTH production Osteomalacia is characterized by lack of bone mineralization treatment may involve correction of calcium, phosphorus , and 25-OH vitamin D levels toward normal values, and mitigation of hyperparathyroidism

38. Declining GFR leads to phosphorus retention. This results in hypocalcemia as phosphorus complexes with calcium, deposits in soft tissues, and stimulates PTH. Loss of renal mass and low 25-OH vitamin D levels often seen in CKD patients result in low 1,25(OH ) vitamin D production by the kidney. Because 1,25(OH) vitamin D is a suppressor of PTH production, hypovitaminosis D also leads to secondary hyperparathyroidism

39. first step in treatment of metabolic bone disease is control of hyperphosphatemia dietary phosphorus restriction initially ( see section on dietary management oral phosphorus binders if targets are not achieved Oral phosphorus binders block absorption of dietary phosphorus in the gut and are given thrice daily with meals

40. Calciumcontaining binders (calcium carbonate, 650 mg/tablet, or calcium acetate, 667 mg/capsule , used at doses of one to three pills per meal) are relatively inexpensive but may contribute to positive calcium balance and vascular calcification ; overt hypercalcemia may also occur current guidelines suggest limiting their use in favor of the non-calcium–containing binders sevelamer carbonate (800–3200 mg/meal) and lanthanum carbonate ( 500–1000 mg/meal )

41. Phosphate Binders Once serum phosphorus levels are controlled, active vitamin D ( 1,25[OH] vitamin D, or calcitriol) or other vitamin D analogs are used by nephrologists to treat secondary hyperparathyroidism in advanced CKD and ESRD. Serum 25- OH vitamin D levels should be measured and brought to normal prior to considering administration of active vitamin D

42. Typical calcitriol dosing is 0.25 or 0.5 mcg orally daily or every other day. Cinacalcet targets the calcium-sensing receptors of the parathyroid gland and suppresses PTH production. Cinacalcet , 30–90 mg orally once a day, can be used if elevated serum phosphorus or calcium levels prohibit the use of vitamin D analogs; cinacalcet can cause serious hypocalcemia, and patients should be closely monitored for this complication

43. Hematologic Complications CKD Anemia Coagulopathy

44. Anemia in CKD due to decreased erythropoietin production Anemia Of Chronic Disease: high levels of hepcidin , which blocks GI iron absorption and mobilization of iron from body stores thyroid function tests, serum vitamin B 12 levels, and iron stores (ferritin and iron saturation) should be checked In CKD, a serum ferritin below 100–200 ng/mL or iron saturation less than 20% is suggestive of iron deficiency

45. Iron stores may be repleted with oral or parenteral iron; iron therapy should probably be withheld if the serum ferritin is greater than 500–800 ng/mL, even if the iron saturation is less than 20 %. Oral therapy with ferrous sulfate, gluconate, or fumarate, 325 mg once daily , is the initial therapy In pre-ESRD CKD those who do not respond due to poor GI absorption or lack of tolerance, intravenous iron ( eg , iron sucrose or iron gluconate ) may be necessary

46. Erythropoiesis-stimulating agents (ESAs, eg , recombinant erythropoietin [ epoetin alfa or beta] and darbepoetin ) are used to treat the anemia of CKD if other treatable causes are excluded starting dose of epoetin alfa is 50 units/kg (3000–4000 units/dose) once or twice a week, and darbepoetin is started at 0.45 mcg/kg and administered every 2–4 weeks; epoetin beta is given every 2–4 weeks

47. ESAs Intravenous Subcutaneous darbopoetin Hypertension is a common complication of treatment with ESAs

48. Coagulopathy bleeding diathesis that may occur in stage 4–5 CKD is mainly due to platelet dysfunction Treatment is required only in patients who are symptomatic Desmopressin (25 mcg intravenously every 8–12 hours for two doses ) is a short-lived but effective treatment for platelet dysfunction and it is often used in preparation for surgery or kidney biopsy Dialysis improves the bleeding time

49. Hyperkalemia stages 4–5 Cardiac monitoring is indicated for any ECG changes seen with hyperkalemia or a serum potassium level greater than 6.0–6.5 mEq /L or mmol /L Chronic hyperkalemia is best treated with dietary potassium restriction (2 g/day) and minimization or elimination of any medications that may impair renal potassium excretion Diuretics

50. Acid Base Disorders Damaged kidneys are unable to excrete the 1 mEq /kg/day of acid generated by metabolism of dietary animal proteins in the typical Western diet Metabolic Acidosis Decreased GFR proximal or distal tubular defects may contribute to or worsen the acidosis Excess hydrogen ions are buffered by bone; the consequent leaching of calcium and phosphorus from the bone contributes to the metabolic bone disease

51. Chronic acidosis can also result in muscle protein catabolism as well as growth retardation in children with CKD and may accelerate progression of CKD Reduction of dietary animal protein and increased fruit and vegetable intake, and the administration of oral sodium bicarbonate (in doses of 0.5–1.0 mEq /kg/day divided twice daily and titrated as needed) are strategies to bring serum bicarbonate levels toward normal

52. Neurologic Complications Uremic encephalopathy does not occur until GFR falls below 5–10 mL/min/1.73 m2 Symptoms begin with difficulty in concentrating and can progress to lethargy, confusion, seizure, and coma . Physical findings may include altered mental status, weakness, and asterixis . These findings improve with dialysis peripheral neuropathies (stocking-glove or isolated mononeuropathies ), erectile dysfunction, autonomic dysfunction, and restless leg syndrome These may not improve with dialysis therapy

53. Endocrine Complicaions Decreased renal elimination of insulin in advanced CKD confers risk for hypoglycemia in treated diabetic patients Doses of oral hypoglycemics and insulin may need reduction. The risk of lactic acidosis with metformin is due to both dose and eGFR ; it should be discontinued when eGFR is less than 30 mL/min/1.73 m2 Decreased libido and erectile dysfunction are common

54. Men have decreased testosterone levels; women are often anovulatory . Women with serum creatinine less than 1.4 mg/ dL are not at increased risk for poor outcomes in pregnancy; however, those with serum creatinine greater than 1.4 mg/ dL may experience faster progression of CKD with pregnancy pregnancy can occur in this setting; however, fetal mortality approaches 50%, and babies who survive are often premature

55. Treatment Slowing Progression Dietary modification Medical Management Management of ESRD

56. Slowing the Progress Treat underlying cause CKD Control of diabetes should be aggressive in early CKD Blood pressure control is vital to slow progression of all forms of CKD ; agents that block the renin-angiotensin-aldosterone system are particularly important in proteinuric patients. Obese patients :lose weight. Risks for AKI should be minimized or avoided. treatment of metabolic acidosis and of hyperuricemia

57. Goals of Care in CKD Slow decline in kidney function Blood pressure control 1 ACR <30 mg/g: ≤140/90 mm Hg ACR 30-300 mg/g: ≤130/80 mm Hg* ACR >300 mg/g: ≤130/80 mm Hg Individualize targets and agents according to age, coexistent CVD, and other comorbidities ACE or ARB * Reasonable to select a goal of 140/90 mm Hg, especially for moderate albuminuria (ACR 30-300 mg/g.) 2 Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. Kidney Int Suppl . (2012 );2:341-342. KDOQI Commentary on KDIGO Blood Pressure Guidelines. Am J Kidney Dis . 2013;62:201-213.

58. Slowing CKD Progression: ACEi or ARB Risk/benefit should be carefully assessed in the elderly and medically fragile Check labs after initiation If less than 25% SCr increase, continue and monitor If more than 25% SCr increase , stop ACEi and evaluate for RAS Continue until contraindication arises, no absolute eGFR cutoff Better proteinuria suppression with low Na diet and diuretics Avoid volume depletion Avoid ACEi and ARB in combination 1,2 Risk of adverse events (impaired kidney function, hyperkalemia) Kunz R, et al. Ann Intern Med . 2008;148:30-48. Mann J, et al. ONTARGET study. Lancet . 2008;372:547-553.

59. Goals of Care in CKD: Glucose Control Target HbA1c ~7.0 % Can be extended above 7.0% with comorbidities or limited life expectancy, and risk of hypoglycemia Risk of hypoglycemia increases as kidney function becomes impaired Declining kidney function may necessitate changes to diabetes medications and renally -cleared drugs NKF KDOQI . Diabetes and CKD: 2012 Update. Am J Kidney Dis . 2012 60:850-856.

60. Modification of Other CVD Risk Factors in CKD Smoking cessation Exercise Weight reduction to optimal targets Lipid lowering therapy In adults >50 yrs , statin when eGFR ≥ 60 ml/min/1.73m 2 ; statin or statin/ ezetimibe combination when eGFR < 60 ml/min/1.73m 2 In adults < 50 yrs , statin if history of known CAD, MI, DM, stroke Aspirin is indicated for secondary but not primary prevention Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group . Kidney Int Suppls . 2013;3:1-150 .

61. Detect and Manage CKD Complications Anemia Initiate iron therapy if TSAT ≤ 30% and ferritin ≤ 500 ng/mL (IV iron for dialysis, Oral for non-dialysis CKD) Individualize erythropoiesis stimulating agent (ESA) therapy: Start ESA if Hb <10 g/dl, and maintain Hb <11.5 g/dl. E nsure adequate Fe stores. Appropriate iron supplementation is needed for ESA to be effective CKD-Mineral and Bone Disorder (CKD-MBD) Treat with D3 as indicated to achieve normal serum levels 2000 IU po qd is cheaper and better absorbed than 50,000 IU monthly dose. Limit phosphorus in diet (CKD stage 4/5), with emphasis on decreasing packaged products - Refer to renal RD May need phosphate binders

62. Detect and Manage CKD Complications Metabolic acidosis Usually occurs later in CKD Serum bicarb >22mEq/L Correction of metabolic acidosis may slow CKD progression and improve patients functional status 1,2 Hyperkalemia Reduce dietary potassium Stop NSAIDs, COX-2 inhibitors, potassium sparing diuretics ( aldactone ) Stop or reduce beta blockers, ACEi /ARBs Avoid salt substitutes that contain potassium Mahajan, et al. Kidney Int . 2010;78:303-309. de Brito- Ashurst I, et al. J Am Soc Nephrol . 2009;20:2075-2084.

63. Dietary Managment Salt and water Restriction Intake of greater than 3–4 g/day can lead to hypertension and hypervolemia, whereas intake of less than 1 g/day can lead to volume depletion and hypotension. A goal of 2 g/day of sodium is reasonable for most patients Protein Restriction Reduced intake of animal protein to 0.6–0.8 g/kg/day may slow CKD progression and is likely not harmful in the otherwise well-nourished patient

64. Potassium Restriction Restriction is needed once the GFR has fallen below 10–20 mL/min/1.73 m2, or earlier if the patient is hyperkalemic should limit their intake to less than 50–60 mEq /day (2 g/day). An aggressive bowel regimen should be instituted for patients with hyperkalemia (more than two bowel movements daily), since a higher percentage of potassium is excreted through the GI tract as GFR declines

65. Phosphorus Restriction Guidelines suggest lowering elevated serum phosphorus levels toward normal in all stages of CKD. Dietary phosphate restriction to 800–1000 mg/day is the first step Processed foods and cola beverages are often preserved with highly bioavailable phosphorus and should be avoided. Foods rich in phosphorus such as eggs, dairy products, nuts, beans, and meat may also need to be limited, although care must be taken to avoid protein malnutrition. When GFR is less than 20–30 mL/min/1.73 m2, dietary restriction is rarely sufficient to reach target levels, and phosphorus binders are usually required

66. Medical Managment Dosages of drugs should be adjusted for GFR. Insulin doses may need to be decreased Magnesium-containing medications , such as laxatives or antacids, and phosphorus-containing medicines ( eg , cathartics) should be avoided. Active morphine metabolites can accumulate in advanced CKD; this problem is not encountered with other opioid agents. Drugs with potential nephrotoxicity (NSAIDs, intravenous contrast, as well as others noted in the Acute Kidney Injury section) should be avoided

67. Common Medications Requiring Dose Reduction in CKD Allopurinol Gabapentin CKD 4- Max dose 300mg qd CKD 5- Max dose 300mg qod Reglan Reduce 50% for eGFR < 40 Can cause irreversible EPS with chronic use Narcotics Methadone and fentanyl best for ESRD patients Lowest risk of toxic metabolites

68. Renally cleared beta blockers Atenolol , bisoprolol , nadolol Digoxin Some Statins Lovastatin , pravastatin , simvastatin . Fluvastatin , rosuvastatin Antimicrobials Antifungals, aminoglycosides, Bactrim, Macrobid Enoxaparin Methotrexate Colchicine

69. Treatment of ESRD Dialysis Hemodialysis Peritoneal dialysis Kidney transplant Medical managment

70. Treatment of ESRD GFR declines to 5–10 mL/min/1.73 m2, renal replacement therapy (hemodialysis , peritoneal dialysis, or kidney transplantation) is required to sustain life Referral to a nephrologist should take place in late stage 3 CKD, or when the GFR is declining rapidly .

71. Dialysis should be considered when GFR is near 10 mL/min/1.73 m2 uremic symptoms are present Fluid overload unresponsive to diuresis refractory hyperkalemia Acidosis pH< 7.1

72. Hemodialysis Vascular access : arteriovenous fistula (the preferred method) or prosthetic graft indwelling catheter Infection, thrombosis, and aneurysm formation are complications seen more often in grafts than fistulas Staph Aureus three times a week, 3-5 hour Home hemodialysis is often performed more frequently (3–6 days per week for shorter sessions ) and requires a trained helper

73. Peritoneal Dialysis peritoneal membrane is the “dialyzer.” Dialysate is instilled into the peritoneal cavity through an indwelling catheter; water and solutes move across the capillary bed that lies between the visceral and parietal layers of the membrane into the dialysate during a “dwell.” After equilibration, the dialysate is drained, and fresh dialysate is instilled—this is an “exchange.

74. Common Complication: Peritonitis nausea and vomiting, abdominal pain, diarrhea or constipation , and fever The normally clear dialysate becomes cloudy; and a diagnostic peritoneal fluid cell count greater than 100 white blood cells/ mcL with a differential of greater than 50% polymorphonuclear neutrophils is present Staph Aureus and Streptococci and Gram – either vancomycin or a first-generation cephalosporin (cefazolin ) plus a third-generation cephalosporin ( ceftazidime ) Culture Results

75. Kidney Transplantation Many patients with ESRD are otherwise healthy enough to be suitable for transplantation

76. Medical Managment some patients are not candidates for kidney transplantation and may not benefit from dialysis patients with ESRD who elect not to undergo dialysis or who withdraw from dialysis, progressive uremia with gradual suppression of sensorium results in a painless death within days to months

77. Hyperkalemia may intervene with a fatal cardiac dysrhythmia. Diuretics, volume restriction, and opioids may help decrease the symptoms of volume overload. Involvement of a palliative care team is essential

78. Prognosis most common cause of death is cardiac disease (more than 50%) Others are infection, cerebrovascular disease, and malignancy. Diabetes, advanced age, a low serum albumin, lower socioeconomic status, and inadequate dialysis are all significant predictors of mortality; high FGF-23 levels are a marker for mortality in ESRD

79. When to Refer A patient with stage 3–5 CKD should be referred to a nephrologist for management in conjunction with the primary care provider. A patient with other forms of CKD such as those with proteinuria greater than 1 g/day or polycystic kidney disease should be referred to a nephrologist at earlier stages

80. * Significant albuminuria is defined as ACR ≥300 mg/g (≥30 mg/ mmol ) or AER ≥300 mg/24 hours, approximately equivalent to PCR ≥500 mg/g (≥50 mg/ mmol ) or PER ≥500 mg/24 hours ** Progression of CKD is defined as one or more of the following: 1) A decline in GFR category accompanied by a 25% or greater drop in eGFR from baseline; and/or 2) rapid progression of CKD defined as a sustained decline in eGFR of more than 5ml/min/1.73m 2 /year. KDOQI US Commentary on the 2012 KDIGO Evaluation and Management of CKD Indications for Referral to Specialist Kidney Care Services for People with CKD Acute kidney injury or abrupt sustained fall in GFR GFR <30 ml/min/1.73m 2 (GFR categories G4-G5) Persistent albuminuria (ACR > 300 mg/g)* Atypical Progression of CKD ** Urinary red cell casts, RBC more than 20 per HPF sustained and not readily explained Hypertension refractory to treatment with 4 or more antihypertensive agents Persistent abnormalities of serum potassium Recurrent or extensive nephrolithiasis Hereditary kidney disease

81. When to Admit Admission should be considered for decompensation of problems related to CKD , such as worsening of acid-base status, electrolyte abnormalities, and volume overload, that cannot be appropriately treated in the outpatient setting. Admission is appropriate when a patient needs to start dialysis and is not stable for its outpatient initiation