RENAL DISEASE: CKD

CHRONIC KIDNEY DISEASE

• Progressive, irreversible deterioration of renal function

• LONG standing disease, usually resulting from an untreated AKI

CHRONIC KIDNEY DISEASE

• Defined as

• kidney damage or GFR of 60 mL/min/1.73 m² for three months

POSSIBLE CAUSES / RISK FACTORS OF CKD

• diabetes

• hypertension

• age >60

• smoking

• obesity

• family history

• heart disease

SIGNS AND SYMPTOMS OF CKD

CENTRAL NERVOUS SYSTEM

• Confusion

• Seizures 

• Coma

SIGNS AND SYMPTOMS OF CKD

RENAL

• Polyuria

• Nocturia

• Sodium + Water Retention

SIGNS AND SYMPTOMS OF CKD

HORMONAL

• Infertility

• Loss of libido

• Amenorrhoea

• Impotence

SIGNS AND SYMPTOMS OF CKD

BONE

• Osteomalacia

• pain

• Osteosclerosis 

• Hyperparathroidism

SIGNS AND SYMPTOMS OF CKD

CARDIOVASCULAR SYSTEM

• Hypertension

• Heart Failure

• Pericarditis 

• Vascular disease

• Peripheral oedema

SIGNS AND SYMPTOMS OF CKD

GASTROINTESTINAL TRACT

• Nausea 

• Vomiting

• Weight Loss

SIGNS AND SYMPTOMS OF CKD

PERIPHERAL NEUROPATHY

Stage 1

• Kidney damage- normal GFR

• ≥90 mL/min/1.73m²

stage 2

• Kidney damage-mild ⭣GFR

• 60-89 mL/min/1.73m²

stage 3

• Moderate ⭣GFR

• 30-59 mL/min/1.73m²

stage 4

• Severe ⭣GFR

• 15-29 mL/min/1.73m²

stage 5

• End-stage renal disease

• <15 mL/min/1.73m² (or dialysis)

STAGES IN PROGRESSION OF CHRONIC KIDNEY DISEASE AND THERAPEUTIC STRATEGIES

• stage 1

• normal

• Screening for CKD risk factors

STAGES IN PROGRESSION OF CHRONIC KIDNEY DISEASE AND THERAPEUTIC STRATEGIES

• stage 2

• increased risk

• CKD risk reduction

• Screening for CKD

STAGES IN PROGRESSION OF CHRONIC KIDNEY DISEASE AND THERAPEUTIC STRATEGIES

• stage 3

• Damage

• Diagnosis & treatment

• Treat comorbid conditions

• Slow progression

STAGES IN PROGRESSION OF CHRONIC KIDNEY DISEASE AND THERAPEUTIC STRATEGIES

• stage 4

• ⭣GFR

• Estimate progression 

• Treat complications

• Prepare for replacement

STAGES IN PROGRESSION OF CHRONIC KIDNEY DISEASE AND THERAPEUTIC STRATEGIES

• stage 5

• Kidney failure

• Replacement by 

  • Dialysis

  • Transplantation

STAGES IN PROGRESSION OF CHRONIC KIDNEY DISEASE AND THERAPEUTIC STRATEGIES

• stage 6

CKD death

MEASUREMENT OF RENAL FUNCTION

• gfr

• creatinine clearance

• urea

GFR

• volume of filtrate produced by the glomeruli of both kidneys each minute

• reliable indicator of renal function

Creatinine Clearance

• eGFR equations for Adult & Pediatric patients

  • Modification of Diet in Renal Disease (MDRD)

  • Cockcroft-Gault

  • CKD-Epidemiology Collaboration (CKD-EPI) 

  • Schwartz

  • Counahan-Baratt

MDRD EQUATION

• Step 1: Determine if the patient has CKD.

• Step 2: Check serum creatinine and calculate creatinine clearance (consider age and weight).

• Step 3: Adjust medication based on clearance and literature guidelines.

  • Based on literature, 20-30 mL of serum creatinine clearance, adjust the medication to q8h; if 31-40 mL, give q12h. 

COCKCROFT-GAULT EQUATION

men

COCKCROFT-GAULT EQUATION

women

COCKCROFT-GAULT EQUATION

CKD-EPI EQUATION

SCHWARTZ FORMULA

k = 0.45

Infants < 1 year of age

k = 0.55

Children and adolescent females

k = 0.7

Adolescent males

COUNAHAN-BARRATT EQUATION

CLINICAL EVALUATION

• physical findings: metabolic abnormalities

• Hypo/hypernatremia

• Metabolic acidosis

• Hyperparathyroidism

CLINICAL EVALUATION

• physical findings: neurological manifestations

• Short attention span

• Loss of memory

• Confusion

• Seizures 

• Peripheral neuropathy

• Pain

• Burning sensation

CLINICAL EVALUATION

• physical findings: cardiovascular problems

• Peripheral edema

• Arterial HTN

• CHF

CLINICAL EVALUATION

• physical findings: respiratory problems

• Dyspnea

• pulmonary edema

CLINICAL EVALUATION

• physical findings: gi manifestations

• Hiccups

• Nausea and Vomiting

• Constipation

• Anorexia

• Stomatitis

CLINICAL EVALUATION

• physical findings: integumentary findings

• Pale

• Dry scaly skin

• Severe itching

• Brittle nails or hair

CLINICAL EVALUATION

• physical findings: musculoskeletal changes

• Bone pain

CLINICAL EVALUATION

• physical findings: hematologic disturbances

• Anemia

• Easy bruising

• Pallor skin

CLINICAL EVALUATION

• diagnostic test result

• Ultrasonography

• IV Urography (IVU)

• Plain abdominal radiography

• Mercaptoacetyltriglycine (MAG3)

• Dimercaptosuccinic acid (DMSA)

• Computed Tomography (CT)

• Magnetic Resonance Imaging (MRI)

• Magnetic Resonance Angiography (MRA)

• Renal biopsy

TREATMENT OBJECTIVES

1. Avoid conditions that might worsen renal failure

2. Treat the secondary complications

3. Relieve symptoms

4. Implement regular dialysis treatment and/or transplantation at the most appropriate time

COMORBIDITIES

• Hypertension

• Edema

• GI disturbances

• Skin problems

• Anemia

• Metabolic disturbances

HYPERTENSION

treatment

• ace/arbs

• ccb

• beta blockers

• selective alpha 1 blocker

• vasodilators

• centrally acting drug

ACEI and ARBs

• Treatment for all diabetic patients with micro or macroalbuminuria and CKD, regardless of the BP

• Reduction in GFR by preventing angiotensin II-mediated vasoconstriction of the efferent glomerular arteriole

CALCIUM CHANNEL BLOCKERS

• DOC for patients with proteinuria

• Vasodilatation: reduced Ca influx into vascular muscle cells

• Promote sodium excretion associated with fluid overload

BETA-BLOCKERS

• Use the cardio-selective β-blockers (atenolol, metoprolol)

Atenolol

• renal excretion

• dosage adjustment required

Metoprolol: 

• liver excretion

• no dosage adjustment required

SELECTIVE ALPHA 1 BLOCKER

• Produce improvements in insulin sensitivity, adverse lipid profiles and prostate hypertrophy obstruction

Used rarely because of side effect: development of heart failure

VASODILATORS

Used as an alternative when other measures are inadequate

VASODILATORS

drugs

• Hydralazine, Minoxidil

CENTRALLY ACTING DRUG

Rarely used because of adverse effect

CENTRALLY ACTING DRUG

drugs

• Methyldopa, Clonidine

EDEMA

• dietary modifications

• diuretics

DIURETICS

• Loop diuretics: Furosemide > 250 mg/day (advanced cases) - First-line for edema

• Spironolactone with ACEI/ARBS in reducing proteinuria (raise hyperkalemia risk)

DIETARY MODIFICATION

Sodium and potassium restriction

GI DISTURBANCES

Antiemetic

• help control nausea and vomiting

GI DISTURBANCES

• docusate sodium, methylcellulose, enema

prevent constipation

SKIN PROBLEMS

Diphenhydramine:

antipruritic to alleviate itching

ANEMIA

• iron folate supplement

• Recombinant Human Erythropoietin (Epoetin alfa and beta, SQ)

• Novel Erythropoiesis

Novel Erythropoiesis

Stimulating Protein (Darbepoetin alfa)

METABOLIC DISTURBANCES

• acidosis

• hyperphosphatemia

• hypocalcemia

ACIDOSIS

Oral doses of sodium bicarbonate (1–6 g/day)

HYPERPHOSPHATEMIA

• Dietary phosphate restriction

• Administration of phosphate binder (aluminum hydroxide, calcium acetate, calcium carbonate, sevelamer)

HYPOCALCEMIA

• Oral calcium salt, vitamin D

RENAL TRANSPLANT

• Treatment of choice for patients with ESRD who are fit to receive

RENAL TRANSPLANT

• considerations

lderly, comorbidities, tolerate immunosuppressive drugs

RENAL TRANSPLANT

notes

• Donor kidneys supply — living or cadaver

• Histocompatibility

• Immunosuppressants

TRANSPLANT REJECTION TYPES

hyperacute

Immediate, graft loss within minutes–hours after transplantation

TRANSPLANT REJECTION TYPES

hyperacute: symptoms (intra-op)

Acute urine flow cessation and bluish or mottled kidney discoloration

TRANSPLANT REJECTION TYPES

hyperacute: symptoms (post-op)

Fever, anuria, local pain, sodium retention, and hypertension

TRANSPLANT REJECTION TYPES

hyperacute: treatment

Immediate nephrectomy

TRANSPLANT REJECTION TYPES

acute

4–60 days after transplantation

TRANSPLANT REJECTION TYPES

chronic

>60 days after transplantation

TRANSPLANT REJECTION TYPES

chronic: symptoms

• Low-grade fever

• increased proteinuria

• Azotemia

• Hypertension

• Oliguria

• Weight gain

• Edema

TRANSPLANT REJECTION TYPES

chronic: treatment

• Give immunosuppressing agents: Alkylating agents, cyclosporine, antilymphocyte globulin, and corticosteroids

In some cases: nephrectomy

IMMUNOSUPPRESSANTS

goals

1. Maximize kidney function

2. Minimize rejection risk

3. Mitigate risk of adverse effects

IMMUNOSUPPRESSANTS

2 phases

• induction immunosuppression

• maintenance immunosuppression

INDUCTION IMMUNOSUPPRESSION

• Protect the transplant from the high immunological risk that is present in the first few weeks after surgery

• Targets specific immune cells or pathways to rapidly suppress immune response

MAINTENANCE IMMUNOSUPPRESSION

Provide long-term immunosuppression to prevent both acute and chronic rejection, more broadly and continuously

TRANSPLANT MEDICATION

Anti Rejection Steroid

• Tacrolimus (Prograf)- 0.5 mg; 1 mg; 5 mg

• Mycophenolate mofetil (Mycolate)- 250mg

• prednisolone- 5mg

Tacrolimus (Prograf)- 0.5 mg; 1 mg; 5 mg

• Dose varies depending on levels, take at 10am and 10pm

• Should be taken on an empty stomach i.e. 1 hour before or 2 hours after food

• Do not take prior to blood level being taken on day of clinic visit

Mycophenolate mofetil (Mycolate)- 250mg

• Take 2 caps at 10am and 10pm

• Chemist may supply 500mg tab (purple tablet)

• Dose may be increased by Renal Team

• The only brands you should receive are Mycolate or Cellcept if the chemist cannot supply Mycolat

prednisolone- 5mg

• Take 4 tabs at 10am

• Dose will be reduced by Renal Physician after discharge

• Also available in enteric coated tablets

TRANSPLANT MEDICATION

Antibacterial to prevent PCP Pneumonia:

Co-trimoxazole (Septrin)

• 450 mg

• 1 tab at night

TRANSPLANT MEDICATION

Antiviral to prevent CMV infections:

Valganciclovir (Valcyte)

• 450 mg

• Not all patients will require this therapy

• Dose is dependent upon renal function

• Initial dose is usually 1 tablet three times a week. This may increase to 1-2 tablets once daily as renal function improves

TRANSPLANT MEDICATION

To protect the stomach:

ranitidine 150 mg

• Certain patients will continue on PPI therapy e.g. Lanzaprole, Omeprazole, and not receive Ranitidine

TRANSPLANT MEDICATION COMBINATIONS

• steroids

• ciclosporin

• tacrolimus

• sirolimus

• mycophenolate

• azathioprine

• muromonab (OKT3, Mouse monoclonal anti-CD3)

• POLYCLONAL HORSE/RABBIT ANTITHYMOCITE or ANTILYMPHOCYTE GLOBULIN (ATG, ALG)

• HUMANISED or CHIMAERIC ANTI-CD25 (Basiliximab, Daclizumab)

STEROIDS

Bind to steroid receptors and inhibit gene transcription and function of T-cells, macrophages, and neutrophils

CICLOSPORIN

• Forms complex with intracellular protein cyclophilin → inhibits calcineurin

• Ultimately inhibits interleukin-2 synthesis and T-cell activation

TACROLIMUS

Forms complex with an intracellular protein → inhibits calcineurin

SIROLIMUS

Inhibits interleukin-2 cell signaling → blocks T-cell cycling and inhibits B-cells

MYCOPHENOLATE

Inhibits inosine monophosphate dehydrogenase → reduces nucleic acid synthesis → inhibits T- and B-cell function

AZATHIOPRINE

Incorporated as a purine in DNA → inhibits lymphocyte and neutrophil proliferation

MUROMONAB (OKT3, Mouse monoclonal anti-CD3)

• Binds to CD3 complex → blocks, inactivates or kills T-cell

Short t_1/2

POLYCLONAL HORSE/RABBIT ANTITHYMOCITE or ANTILYMPHOCYTE GLOBULIN (ATG, ALG)

Antibodies against lymphocyte proteins → alter T- and B-cell activity

HUMANISED or CHIMAERIC ANTI-CD25 (Basiliximab, Daclizumab)

Monoclonal antibodies that bind CD25 in interleukin-2 complex → prevent T-cell proliferation